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Biomedical subjects

A Thompson

Publications and source records attributed to A Thompson.

At least 163 records · Page 9Linked to original sources
PubMed1996

Efficient vasoactive intestinal polypeptide hydrolyzing autoantibody light chains selected by phage display.

An immunoglobulin light chain (L chain) library derived from the peripheral blood lymphocytes of a patient with asthma was cloned into a phagemid vector. Phage particles displaying L chains capable of binding vasoactive intestinal polypeptide (VIP) were isolated by affinity chromatography. Two VIP binding L chains were expressed in Escherichia coli in soluble form and purified to electrophoretic homogeneity by metal chelating and protein L affinity chromatography. Both L chains catalyzed the hydrolysis of [tyr10-125I]VIP substrate. The catalytic activity eluted at the molecular mass of the monomer form of the L chain (28 kDa) from a gel filtration column. The activity was bound by immobilized anti-kappa-chain antibody. A control recombinant L chain displayed no catalytic activity. Hydrolysis of VIP by the catalytic L chains was saturable and consistent with Michaelis-Menten kinetics. The turnover of the L chains was moderate (0.22 and 2.21/min) and their Km values indicated comparatively high affinity recognition of VIP[111 and 202 nM), producing catalytic efficiencies comparable to or greater than trypsin. Unlike trypsin, the L chains did not display detectable cleavage of casein, suggesting a catalytic activity specialized for VIP. Comparisons of the nucleotide sequences of the L chain cDNA with their putative germ-line counterparts suggested the presence of several replacement mutations in the complementarity determining regions (CDRs). These observations suggest: (a) Retention or acquisition of catalytic activity by the L chains is compatible with affinity maturation of antibodies; and (b) The autoimmune L chain repertoire can serve as a source of substrate-specific and efficient catalysts.

Amino Acid Sequence↗
PubMed1996

A Novel Technique for Accurate Intensity Calibration of Area X-ray Detectors at Almost Arbitrary Energy.

A novel intensity uniformity calibration method for area X-ray detectors is described. In diffraction experiments, amorphous lithium glass plates, containing doping elements chosen for their K edges just below the energy of the main beam, replace the crystallographic samples for the calibration measurement. The fluorescent emission excited by the X-ray beam is almost isotropic. It has exactly the same geometry as the diffracted radiation, and can be obtained at the same wavelength by proper selection of the element and excitation energy. A sample 2theta scan allows the emission distribution as a function of angle to be characterized with an accuracy of a fraction of a percent. This allows a flat-field correction of similar accuracy. The quality of crystallographic data collected with an X-ray image intensifier/CCD detector was significantly improved by flat-field correction using an Sr-doped lithium tetraborate glass. This technique can be applied to X-ray energies from 5 to 50 KeV; the calibration sample is small, stable and easily handled.

Journal Article↗
PubMed1996

Clinical outcomes assessment in multiple sclerosis.

This article represents initial deliberation of an international task force appointed by the US National Multiple Sclerosis Society to develop recommendations for optimal clinical assessment tools for multiple sclerosis clinical trials. Presented within this article are the key issues identified by the task force during its initial year of deliberation. These include the precise purpose for a clinical assessment tool, the clinical dimensions to be measured in a multidimensional outcome measure, desirable attributes of an optimal clinical outcome measure, the complexities of multidimensional outcome measures, the relative merits of categorical clinical ratings and quantitative functional assessments, and a number of other important design issues that relate to the use of a multidimensional outcome measure. An action plan for analysis of existing data is summarized, as are the plans for more detailed recommendations from the task force.

Clinical Trials as Topic↗
PubMed1996

A new transgenic mouse model for the study of cell cycle control in megakaryocytes.

During the development of the megakaryocytic lineage, the megakaryoblasts give rise to megakaryocytes which undergo repeated S phases in the absence of cytokinesis (endomitosis). The cellular oncogene myc plays a central role in the proliferation and differentiation of several cell types. In a previous study, we generated transgenic mice carrying c-myc fused to the estrogen receptor under the control of the platelet factor four (PF4) megakaryocyte-specific promoter. The bone marrow of female transgenic mice, but not of male mice, displayed increased megakaryopoiesis. Here we report that beta-estradiol-induced activation of c-myc in cultured bone marrow cells derived from male or female transgenic mice resulted in prolonged survival of the cells in vitro. Addition of a cocktail of hemopoietic growth factors to beta-estradiol-treated cells, including interleukin 6 (IL-6), IL-3 and stem cell factor further improved the survival time in culture and increased the percentage of large mature cells, but did not result in immortalization. The majority of these PF4-expressing cells, however, did not reach the differentiation stage at which acetylcholinesterase is expressed and did not appear as large megakaryocytes. We conclude that cultured megakaryocytes overexpressing myc are induced to proliferate, but have a limited potential to fully differentiate. Under these conditions, cyclin D3 was downregulated while the level of cyclin A was slightly upregulated.

Acetylcholinesterase↗
PubMed1996

Learning from the community about barriers to health care.

One of the major challenges facing obstetrician-gynecologists, especially those serving populations that are diverse in culture and circumstances, is to identify and address the barriers that keep women from seeking timely preventive and prenatal health care. The Department of Obstetrics and Gynecology at Rochester General Hospital held a community focus groups to learn more about women's attitudes toward health care. In addition to economic issues, such as lack of insurance and an inability to pay, the organizers found that many of the factors that prevent or discourage women from seeking health care involve issues of communication and understanding. Many women wanted what they perceived to be additional services. In reality, many of the things desired involved changes in doctor-patient interactions rather than the addition of any new service, and could be addressed with relative ease and minimal cost. Providing staff members with training in cultural sensitivity and encouraging them to develop a real awareness of patient circumstances are first steps that can lead to better communication between provider and patient and to the development of mutual trust. Other factors, such as the fear of incarceration or of losing one's children if health care is sought, present more serious challenges. Providers of care to high-risk, impoverished populations need to develop strong links to mental health, substance abuse, and family preservation services that allow them to intervene with troubled women and their families with services that are alternatives to incarceration and punitive actions.

Attitude to Health↗
PubMed1996

Diaphragmatic hernia and associated anemia: response to surgical treatment.

From 1985 to 1993, 49 patients (35 women and 14 men) with diaphragmatic hernia and associated anemia underwent surgical repair. The median age was 64.5 years (range 24 to 84 years). Hematologic and gastroenterologic evaluations revealed no other potential cause of bleeding. Each patient had a diaphragmatic hernia. The median time between the diagnosis of anemia and surgical repair was 36 months (range 1 to 334 months). Forty-five patients (91.8%) had received replacement therapy, including iron for 43 and blood transfusions for 32 (median 6 units; range 2 to 70 units). Forty-six patients (93.9%) had symptoms: heartburn in 28, early satiety with bloating in 19, regurgitation in 11, dysphagia in 7, and aspiration in 4. Preoperative upper gastrointestinal endoscopic evaluation demonstrated gastric erosions at the level of the hiatus in 22 patients (44.9%), esophagitis in 7, stenosis in 1, and Barrett's disease in 1. An uncut Collis-Nissen fundoplication was performed in 44 patients, Belsey fundoplication in 2, a cut Collis-Nissen fundoplication, Nissen fundoplication, and Hill repair in 1 each. There was one operative death (2% mortality). Complications occurred in 18 patients (36.7%). Follow-up was complete and ranged from 4 to 103 months (median 63 months). Forty-five patients (91.8%) had resolution of their anemia. Functional results were excellent in 40 patients (81.6%), good in 2 (4.1%), fair in 4 (8.2%), and poor in 3 (6.1%). In most patients with diaphragmatic hernia and associated anemia refractory to medical treatment, surgical repair can result in successful resolution of the anemia.

Adult↗
PubMed1996

Investigation of Z > or = 70 cosmic ray nuclei on the LDEF mission.

The ultra heavy cosmic ray experiment (UHCRE) on the Long Duration Exposure Facility (LDEF) collected approximately 3000 cosmic ray nuclei with Z > 65 in the energy region E > 1.5 GeV/n. Almost 40% of the sample has been analysed to date. Details of the overall charge abundance pattern is outlined with estimates of the actinide abundance.

Actinoid Series Elements↗
PubMed1996

Effects of nitric oxide inhibition on systemic and renal hemodynamics in the hemorrhaged rat.

The systemic and renal hemodynamic responses to nitric oxide (NO) inhibition with L-Name were compared in both normotensive, normovolemic rats and in rats following acute hemorrhagic hypotension. The mean arterial blood pressure increased in normovolemic as well as in hemorrhaged, hypotensive rats. The systemic vascular resistance also increased in both groups, but the increase was greater in normotensive rats (104 +/- 11%) than in hypotensive rats (64 +/- 14%). The renal vascular resistance also increased more in normotensive rats (189 +/- 20%) than in hypotensive rats (102 +/- 19%; p < 0.05). The glomerular filtration rate was markedly reduced by L-Name in normovolemic rats (from 3.0 +/- 0.1 to 2.1 +/- 0.1 ml/min/300 g), but increased in hemorrhaged rats following L-Name (from 1.8 +/- 0.2 to 2.5 +/- 0.2 ml/min/300 g). In summary, the L-Name-induced increase in vascular resistance is markedly reduced following hemorrhage, suggesting that NO production or availability is reduced. However, the NO production continues in the hemorrhaged rat and contributes substantially to the hypotension and functional renal insufficiency associated with acute severe volume depletion.

Animals↗
PubMed1996

Medication prescribing advice and drug utilization: a review from the United Kingdom.

General Medical Practitioners (GPs) in the United Kingdom are usually the first point of contact with the National Health Service (NHS) for patients. They provide the majority of ambulatory care for their practice population and act as 'gatekeepers' for referral onwards to other services. This article investigates the influence of the purchasing authority prescribing advisors (PAs), including pharmacists and GPs on the prescribing habits in Salford, England, an inner city area in the North of England, close to the city of Manchester. The PAs became known as the prescribing CIA, and used the strategy of Control, progressing to Influence and Autonomy, to develop a mature partnership between the GPs, PAs and other health care professionals. Information collated from prescribing (PACT) data, by the Prescription Pricing Authority, was used to make comparisons between different practices within an area. Savings made by making rational changes in prescribing, were used to enhance practice development for the benefit of patient care.

Data Collection↗
PubMed1996

Pain management in sickle cell disease.

Sickle cell disease is a chronic disorder characterized by painful crises, debilitating complications, and a shortened life span. The pain associated with sickle cell crises is often severe, but poorly managed in many health care settings. The disease process and recommendations for effective pain management in this population of patients are discussed.

Adult↗
PubMed1995

Cloning and functional expression of a metalloendopeptidase from human brain with the ability to cleave a beta-APP substrate peptide.

Using a combination of PCR and hybridization screening, we have isolated a cDNA clone for a metalloendopeptidase (h-MP78) from a human temporal cortex library. This 2.5-kb cDNA encodes a 689-amino acid protein with a predicted molecular mass of approximately 78.5 kDa. The primary structure of h-MP78 exhibits high similarity to those of porcine (94%) and rat (92%) thimet oligopeptidase. Expression of the cDNA in HEK-293 resulted in the production of an active enzyme able to cleave a chromogenic beta-APP derived substrate peptide KTEEISEVKM-P-nitro-anilide. RNA blot analysis of various human tissues revealed one major species of h-MP78 mRNA of approximately 2.55 kb. The highest level of mRNA was found in the brain.

Amino Acid Sequence↗
PubMed1995

Structural basis of cell-cell adhesion by cadherins.

Crystal structures of the amino-terminal domain of N-cadherin provide a picture at the atomic level of a specific adhesive contact between cells. A repeated set of dimer interfaces is common to the structure in three lattices. These interactions combine to form a linear zipper of molecules that mirrors the linear structure of the intracellular filaments with which cadherins associate. This cell-adhesion zipper may provide a mechanism to marshal individual molecular adhesive interactions into strong bonds between cells.

Amino Acid Sequence↗
PubMed1995

Immunoglobulin heavy chain germ-line JH-C mu transcription in human precursor B lymphocytes initiates in a unique region upstream of DQ52.

From human precursor B cells which had both immunoglobulin (Ig) heavy (H) chain loci in germ-line configuration, various IgH chain germ-line transcripts were isolated and sequenced. These transcripts were shown to contain sequences derived from the JH region, the IgH chain enhancer element or the Ig switch region. A number of isolated cDNA clones contained sequences at their 5' end that were derived from a single exon located just upstream of DQ52, designated the mu o' element. Sequence analysis of a 920-bp genomic DNA segment, containing the mu o' exon and its 5' flanking region, revealed the presence of various conserved motifs for DNA-binding proteins, such as E2A, Ets, NF-kappa B and AP-2, which have previously been found in the IgH and L chain enhancers. We propose that the activity of the mu o' element, resulting in germ-line transcription of the DQ52-JH gene segment, is required to generate full accessibility for the V(D)J recombinase.

B-Lymphocytes↗