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Biomedical subjects

P Thompson

Publications and source records attributed to P Thompson.

At least 73 records · Page 4Linked to original sources

Magnetism in nickel and synchrotron beam polarization studied by X-ray diffraction.

The ratio of the magnetic to the charge form factors of nickel has been determined by white-beam X-ray diffraction. The measurements were made on the new UK magnetic scattering beamline (XMaS) on a dipole source at the ESRF. The data comprise the three (h,h,0) reflections (4,4,0), (6,6,0) and (8,8,0) and the seven high-order (h,0,0) reflections (6,0,0) to (18,0,0), which doubles the range of wavevectors compared to previous studies. The data have been analysed using Hartree-Fock free-ion wave functions and core electron polarization effects were included. The results support the interpretation of neutron data obtained at lower momentum transfer for the e(g) and t(2g) orbital occupancies. The polarization of the dipole source is deduced to vary from 99.88 to 99.83% between 5 and 15 keV, respectively. This high value makes it an extremely suitable source for studies of ferromagnetism.

Journal Article↗

Mutations of the NF1 gene in children with juvenile myelomonocytic leukemia without clinical evidence of neurofibromatosis, type 1.

Juvenile myelomonocytic leukemia (JMML) is a pediatric myelodysplastic syndrome that is associated with neurofibromatosis, type 1 (NF1). The NF1 tumor suppressor gene encodes neurofibromin, which regulates the growth of immature myeloid cells by accelerating guanosine triphosphate hydrolysis on Ras proteins. The purpose of this study was to determine if the NF1 gene was involved in the pathogenesis of JMML in children without a clinical diagnosis of NF1. An in vitro transcription and translation system was used to screen JMML marrows from 20 children for NF1 mutations that resulted in a truncated protein. Single-stranded conformational polymorphism analysis was used to detect RAS point mutations in these samples. We confirmed mutations of NF1 in three leukemias, one of which also showed loss of the normal NF1 allele. An NF1 mutation was detected in normal tissue from the only patient tested and this suggests that JMML may be the presenting feature of NF1 in some children. Activating RAS mutations were found in four patients; as expected, none of these samples harbored NF1 mutations. Because 10% to 14% of children with JMML have a clinical diagnosis of NF1, these data are consistent with the existence of NF1 mutations in approximately 30% of JMML cases.

Child, Preschool↗

Solid phase synthesis of cyclic peptides: model studies involving i-(i+4) side chain-to-side chain cyclisation.

Conditions for the synthesis of i-(i + 4) side chain-to-side chain head-to-tail Lys-->Glu and Glu-->Lys linked cyclic peptides related to hypoglycaemic analogues of human growth hormone hGH [6-13] have been examined. The success of the cyclisation reaction with the corresponding resin-bound, partially protected linear peptides was found to be both reagent as well as sequence dependent, with competing inter-chain oligomerisation predominating in some cases. The results also indicated that protection with the bulky Fmoc group of the amino acid residues immediately adjacent to the side chain-deprotected Lys and Glu residues, which participate in the cyclisation reaction, enhanced the rate of lactam formation.

Humans↗

Genetic and physical mapping of the Lps locus: identification of the toll-4 receptor as a candidate gene in the critical region.

On the basis of 2093 meioses analyzed in two separate intraspecific backcrosses, the location of the mouse Lpsd mutation was circumscribed to a genetic interval 0.9 cM in size. A total of 19 genetic markers that lie in close proximity to the mutation were examined in mapping. Most of these were previously unpublished polymorphic microsatellites, identified by fragmentation of YAC and BAC clones spanning the region of interest. Lpsd was found to be inseparable from the microsatellite marker D4MIT178, and from three novel polymorphic microsatellites identified near D4MIT178. The mutation was confined between two novel microsatellite markers, herein designated "B" and "83.3." B lies centromeric to the mutation, and was separated by four crossovers in a panel of 1600 mice; 83.3 lies distal to the mutation and was separated by three crossovers in a panel of 493 mice. 66 BAC clones and one YAC clone were assembled to cover > 95% of the critical region. Estimates based on pulsed field gel electrophoresis and fluorescence in situ hybridization indicate that the The B-->83.3 interval is about 3.2 Mb in length. A minimal area of zero recombinational distance from Lpsd was also assigned, and found to occupy approximately 1.2 Mb of physical size. To identify gene candidates, nearly 40,000 sequencing runs were performed across the critical region. Selective hybridization and exon trapping were also employed to identify genes throughout the "zero" region. Only a single intact gene was identified within the entire critical region. This gene encodes the Toll-4 receptor, a member of the IL-1 receptor family.

Animals↗

Quantitative heel ultrasound in 3180 women between 45 and 75 years of age: compliance, normal ranges and relationship to fracture history.

There is growing evidence to support the use of quantitative ultrasound (QUS) to identify fracture risk in late postmenopausal women but few data are available in younger women. In order to address this issue all women between 45 and 75 years of age registered in two general practices in Bournemouth, Dorset, UK were invited to attend for heel QUS. Measurements were made in 79% of the 4018 women identified. The mean QUS results for 5-year age groups were very similar to those from reported reference ranges from North America and the north of England. The odds ratios (95% confidence limits) for self-reported fractures after 45 years per standard deviation of age-adjusted QUS parameters were: broadband ultrasound attenuation (BUA) = 1.40 (1.26-1.56), speed of sound (SOS) = 1.56 (1.41-1.74) and Stiffness = 1.52 (1.37-1.68). The results suggest that QUS is associated with fracture history in early postmenopausal women.

Aged↗

Haemophilus paraphrophilus; a rare cause of intracranial abscess.

We report a case of a 42-year-old man man who presented with neurological symptoms and was found to have an intracranial abscess. A stereotactic aspiration of the abscess yielded a pure growth of Haemophilus paraphrophilus. The patient responded to treatment with cefotaxime. We postulate the mechanism of infection in this patient.

Adult↗

Intraocular pressure change measured by Goldmann tonometry after laser in situ keratomileusis.

PURPOSE: To assess the accuracy of Goldmann tonometry after laser in situ keratomileusis (LASIK). SETTING: University-based refractive surgery group (Clinique du Laser Visuel). METHOD: The database of patients who had LASIK was retrospectively reviewed. Preoperative and postoperative intraocular pressure (IOP) was measured in 145 patients. The correlation between decrease in IOP and various preoperative and intraoperative parameters was evaluated by regression analysis. Only one eye in patients having bilateral surgery was used for statistical analysis. RESULTS: Laser in situ keratomileusis was associated with a mean decrease in IOP of 1.9 mm Hg +/- 2.9 (SD). There was no significant correlation between the decrease and any parameter evaluated. CONCLUSION: Intraocular pressure after LASIK decreased by a mean of 1.9 +/- 2.9 mm Hg. The cause of the decrease remains unknown.

Adult↗

Will elderly rest home residents wear hip protectors?

BACKGROUND: Hip fracture is a common cause of morbidity and mortality in elderly people, for whom osteoporosis, the risk of falling and direct trauma to the hip during the fall are the major risk factors. External hip protectors have been developed which reduce the risk of hip fracture after a fall. However, compliance with their use is uncertain. We addressed this issue in a sample of elderly Dorset rest home residents over a 3-month period. METHODS: 31 rest homes agreed to participate. Of the 288 female subjects approached, 141 gave their informed consent and 101 were allocated to the intervention arm of the study. Their ages ranged from 64 to 98 years, and 44% reported a fall during the preceding 12 months. Each subject was fitted with three pairs of protector pads (Sahvatex, Denmark) sewn into specially designed undergarments. Randomly timed fortnightly visits were made to each subject to assess compliance for 12 weeks. FINDINGS: 27 subjects were compliant for the whole study period; 54 wore the protector pads for less than a week, largely for reasons of poor fitting or discomfort; the remainder withdrew at varying intervals between 1 and 12 weeks. During the study period, there were nine recorded falls onto the hip, six of which occurred in women wearing protectors. None resulted in hip fracture. CONCLUSION: Approximately 50% of elderly rest home residents who are mentally able would wear hip protectors in order to prevent hip fractures. Long-term compliance drops to about 30%. Compliance could be increased substantially if the pads and undergarments were modified to enhance their fit and to reduce the discomfort associated with their use.

Accidental Falls↗

The diagnostic accuracy of bedside and laboratory coagulation: procedures used to monitor the anticoagulation status of patients treated with heparin.

We evaluated the diagnostic accuracy of three bedside coagulation procedures, the Hemochron activated whole-blood clotting time (ACT) (International Technidyne, Edison, NJ), the CoaguChek Plus (Boehringer Mannheim, Indianapolis, Ind) activated partial thromboplastin time (APTT) and the TAS (Cardiovascular Diagnostics, Raleigh, NC) APTT, before removal of arterial sheaths, in patients who received heparin therapy during percutaneous coronary angioplasty. As part of the postprocedure care, nurses performed bedside coagulation tests, removed the sheaths when appropriate coagulation criteria were met, and collected samples for laboratory APTT determinations and heparin assays performed with an automated chromogenic anti-Xa assay. Patients with heparin concentrations of 0.3 U/mL or more were classified as anticoagulated and those with concentrations less than 0.3 U/mL, as not anticoagulated. Analysis of the receiver operator characteristic (ROC) curve was used to rank the performance of the methods. Areas under the ROC curves +/- SE for the laboratory APTT, CoaguChek Plus APTT, Hemochron ACT, and TAS APTT were 0.978 +/- 0.016, 0.872 +/- 0.044, 0.797 +/- 0.039, and 0.795 +/- 0.048, respectively. At cutoff values for the tests that provide greatest safety for the patients (no false-negative results), the false-positive rates for the laboratory, CoaguChek Plus, Hemochron, and TAS methods were 15%, 27%, 62%, and 100%, respectively. The laboratory APTT demonstrated the highest diagnostic accuracy in this application; however, turnaround time for the test (50% of the results were reported in excess of 77 minutes) was inadequate for clinical decision making. To meet this requirement, we developed a point-of-care program using the whole blood APTT performed on the CoaguChek Plus analyzer.

Aged↗

Molecular epidemiology of epithelial tumors.

Within the past year there has been a dramatic increase in the number of molecular epidemiologic studies reported in the literature, particularly those evaluating gene-gene and gene-environment interactions. Molecular epidemiologic studies have become more sophisticated owing to collaborations between laboratory scientists and epidemiologists, and because these studies are now conducted on well-characterized populations with appropriate study design. Although there continue to be inconsistencies across some studies, it is clear that the evaluation of gene-gene and gene-environment interactions can delineate portions of the population who are particularly sensitive to certain carcinogenic exposures, based on polymorphisms in genes involved in preventing and controlling carcinogenesis. Identification of these subsets of susceptible individuals can result in the design of preventive strategies targeting the most "at risk" populations.

Carcinogens↗

A comparison of descriptive characteristics of male outpatients and inpatients with affective disorders.

Recent studies of patients with affective disorders have found that there are biological differences between inpatients and outpatients. Concerned by these findings, we compared individuals admitted to our inpatient and outpatient affective disorders clinical research center who met criteria for major depression. We hypothesized that inpatients would be more severely ill, more suicidal, more functionally impaired, and have more co-morbid disorders and higher ratings of depression and mood state dysfunction. The demographic profiles, lifetime co-morbid Axis I diagnoses, consumption histories, symptom profiles, global assessment of functioning, and severity of current stressors (Axis IV) were compared and contrasted for the two groups. Inpatients had more severe current psychosocial stressors, lower current levels of functioning, increased lifetime co-morbid Axis I diagnoses, and increased rates of psychiatric hospitalizations, however, they did not have higher depression symptom ratings. In conclusion, inpatients and outpatients differed significantly in the severity of their stressors, coping abilities and history of previous hospitalizations, but not in most demographic variables or their current symptoms of depression.

Adaptation, Psychological↗

Exercise, smoking cessation, and short-term changes in serum lipids in women: a preliminary investigation.

PURPOSE: This study investigated the combined effects of exercise and smoking cessation on serum lipids. METHODS: Eighteen female smokers quit smoking using standard behavioral methods combined with exercise (N = 9) or with a nonexercise contact time control (N = 9). The smoking cessation program for both groups consisted of 12 weekly 1-h behavioral modification sessions held over 12 wk. Exercise training consisted of three supervised 45-min sessions per week for 12 wk. Contact control consisted of three health education lectures/discussions per week for 12 wk. Fitness (estimated VO2 peak), dietary variables, and fasting serum lipids and lipoproteins were assessed before and at the end of treatment. VO2 peak increased in the exercise subjects compared with the controls. RESULTS: Total caloric intake as well as total fat and carbohydrate increased significantly after smoking cessation in the controls, but there were no dietary changes in the exercise group. high density lipoprotein (HDL)-C2 increased (7.6 mg x dL(-1), P < 0.01) in the exercise group, whereas the increases in HDL and its subfractions did not attain statistical significance in the contact control group. Total cholesterol, low density lipoprotein (LDL)-C, and triglycerides did not change in either group. CONCLUSIONS: We conclude that exercise training magnifies the increase in HDL-C that usually occurs with smoking cessation.

Adult↗

Heterogeneity of mitochondrial protein biogenesis during primary leaf development in barley

The natural developmental gradient of light-grown primary leaves of barley (Hordeum vulgare L.) was used to analyze the biogenesis of mitochondrial proteins in relation to the age and physiological changes within the leaf. The data indicate that the protein composition of mitochondria changes markedly during leaf development. Three distinct patterns of protein development were noted: group A proteins, consisting of the E1 beta-subunit of the pyruvate dehydrogenase complex, ORF156, ORF577, alternative oxidase, RPS12, cytochrome oxidase subunits II and III, malic enzyme, and the alpha- and beta-subunits of F1-ATPase; group B proteins, consisting of the E1 alpha-subunit of the pyruvate dehydrogenase complex, isocitrate dehydrogenase, HSP70A, cpn60C, and cpn60B; and group C proteins, consisting of the four subunits of the glycine decarboxylase complex (P, H, T, and L proteins), fumarase, and formate dehydrogenase. All of the proteins increased in concentration from the basal meristem to the end of the elongation zone (20.0 mm from the leaf base), whereupon group A proteins decreased, group B proteins increased to a maximum at 50 mm from the leaf base, and group C proteins increased to a maximum at the leaf tip. This study provides evidence of a marked heterogeneity of mitochondrial protein composition, reflecting a changing function as leaf cells develop photosynthetic and photorespiratory capacity.

Journal Article↗

Refining the risk-benefit equation for thrombolysis: how to identify the low risk patient before administering thrombolytic therapy.

In view of the relative risk of intracranial haemorrhage and major bleeding with thrombolytic therapy, it is important to identify as early as possible the low risk patient who may not have a net clinical benefit from thrombolysis in the setting of acute myocardial infarction. An analysis of 5434 hospital-treated patients with myocardial infarction in the Perth MONICA study showed that age below 60 and absence of previous infarction or diabetes, shock, pulmonary oedema, cardiac arrest and Q-wave or left bundle branch block on the initial ECG identified a large group of patients with a 28 day mortality of only 1%, and one year mortality of only 2%. Identification of baseline risk in this way helps refine the risk-benefit equation for thrombolytic therapy, and may help avoid unnecessary use of thrombolysis in those unlikely to benefit.

Age Factors↗

The Cys-rich region of hepatitis A virus cellular receptor 1 is required for binding of hepatitis A virus and protective monoclonal antibody 190/4.

The hepatitis A virus cellular receptor 1 (HAVcr-1) cDNA codes for a class I integral membrane glycoprotein, termed havcr-1, of unknown natural function which serves as an African green monkey kidney (AGMK) cell receptor for HAV. The extracellular domain of havcr-1 has an N-terminal Cys-rich region that displays homology with sequences of members of the immunoglobulin superfamily, followed by a Thr/Ser/Pro (TSP)-rich region characteristic of mucin-like O-glycosylated proteins. The havcr-1 glycoprotein contains four putative N-glycosylation sites, two in the Cys-rich region and two in the TSP-rich region. To characterize havcr-1 and define region(s) involved in HAV receptor function, we expressed the TSP-rich region in Escherichia coli fused to glutathione S-transferase and generated antibodies (Ab) in rabbits (anti-GST2 Ab). Western blot analysis with anti-GST2 Ab detected 62- and 65-kDa bands in AGMK cells and 59-, 62-, and 65-kDa bands in dog cells transfected with the HAVcr-1 cDNA (cr5 cells) but not in dog cells transfected with the vector alone (DR2 cells). Treatment of AGMK and cr5 cell extracts with peptide-N-glycosidase F resulted in the collapse of the havcr-1-specific bands into a single band of 56 kDa, which indicated that different N-glycosylated forms of havcr-1 were expressed in these cells. Treatment of AGMK and cr5 cells with tunicamycin reduced binding of protective monoclonal Ab (MAb) 190/4, which suggested that N-glycans are required for binding of MAb 190/4 to havcr-1. To test this hypothesis, havcr-1 mutants lacking the N-glycosylation motif at the first site (mut1), second site (mut2), and both (mut3) sites were constructed and transfected into dog cells. Binding of MAb 190/4 and HAV to mut1 and mut3 cells was highly reduced, while binding to mut2 cells was not affected and binding to dog cells expressing an havcr-1 construct containing a deletion of the Cys-rich region (d1- cells) was undetectable. HAV-infected cr5 and mut2 cells but not mut1, mut3, d1-, and DR2 cells developed the characteristic cytoplasmic granular fluorescence of HAV-infected cells. These results indicate that the Cys-rich region of havcr-1 and its first N-glycosylation site are required for binding of protective MAb 190/4 and HAV receptor function.

Animals↗

Polymorphisms of the hepatitis A virus cellular receptor 1 in African green monkey kidney cells result in antigenic variants that do not react with protective monoclonal antibody 190/4.

Monoclonal antibody (MAb) 190/4 blocks binding of hepatitis A virus (HAV) to the HAV cellular receptor 1 (havcr-1) and protects African green monkey kidney (AGMK) clone GL37 cells (GL37 cells) against HAV infection. BS-C-1 and CV-1 cells, two widely used AGMK cell lines, did not react with MAb 190/4 but expressed havcr-1, as judged by Western blot analysis. The cDNA coding for havcr-1 was amplified from BS-C-1 and CV-1 total cellular RNA by reverse transcription-PCR. Alignment of the amino acid sequences inferred from the cDNA nucleotide sequences showed that BS-C-1 and CV-1 havcr-1 differed from GL37 havcr-1 by having two substitutions in the Cys-rich region, N48H and K108Q, and 10 to 11 additional substitutions plus the insertion of 18 to 22 amino acids in the mucin-like region. Studies with chimeras of GL37 havcr-1 and BS-C-1 havcr-1 showed that the K108Q substitution was responsible for the lack of reaction of MAb 190/4 with BS-C-1 and CV-1 cells. Binding studies indicated that HAV bound to dog cell transfectants expressing the BS-C-1 havcr-1 as well as the GL37/BS-C-1 havcr-1 chimeras. These results indicate that antigenic variants of havcr-1 are expressed in AGMK cells and that binding of HAV to these havcr-1 variants tolerates changes in protective epitope 190/4.

Amino Acid Sequence↗