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Biomedical subjects

T White

Publications and source records attributed to T White.

At least 73 records · Page 4Linked to original sources

Comparison of teaching the basic electrocardiographic concept of frontal plane QRS axis using the classical versus the orderly electrocardiogram limb lead displays.

This study compares the effectiveness of teaching the calculation of frontal plane QRS axis with the use of the classical versus the orderly electrocardiographic limb lead display. Eighty-three students from two environments were randomized into two groups and were taught to determine frontal plane axis with one of the methods. The accuracy and time to determine the axis were tested on 10 electrocardiograms. In the United States the group using the classical display achieved 4.2 (+/-2.7) correct answers, whereas those using the orderly method achieved 6.8 (+/-3.0) (p = 0.0006). The classical group used 9.2 (+/-2.8) minutes to complete the test, whereas the orderly group needed 7.2 (+/-2.0) minutes (p = 0.015). The results achieved in Sweden were similar. The use of the orderly electrocardiographic limb lead display results in greater diagnostic accuracy in less time than the classical display when determining the frontal plane QRS axis.

Adult↗

A new procedure for establishing functional monoclonal antibodies capable of inhibiting E- or P-selectin-dependent cell adhesion.

Employing a new procedure, we established many monoclonal antibodies (mAbs) which inhibit E- or P-selectin-dependent cell adhesion. One of these mAbs is capable of staining selectin in paraffin-embedded histological sections. The procedure is based on immunization of BALB/c mice with irradiated mouse myeloma NS-1 cells (syngeneic HAT-sensitive fusion partner cells) transfected with cDNA encoding human E- or P-selectin. Resulting NS-1 transfectant cells permanently express human E- or P-selectin as immunogen. The mAbs are useful for detecting selectins by flow cytometric and immunohistological methods, and for inhibiting selectin-dependent adhesion in experimental models. In contrast, the majority of anti-selectin mAbs previously established do not have these capabilities.

Animals↗

Cloning and expression of two human lysophosphatidic acid acyltransferase cDNAs that enhance cytokine-induced signaling responses in cells.

Lysophosphatidic acid (LPA) and phosphatidic acid (PA) are two phospholipids involved in signal transduction and in lipid biosynthesis in cells. LPA acyltransferase (LPAAT), also known as 1-acyl sn-glycerol-3-phosphate acetyltransferase (EC 2.3.1.51), catalyzes the conversion of LPA to PA. In this study, we describe the isolation and characterization of two human cDNAs that encode proteins possessing LPAAT activities. These two proteins, designated here as LPAAT-alpha and LPAAT-beta, contain extensive sequence sequence similarities to microbial or plant LPAAT sequences. LPAAT-alpha mRNA was detected in all tissues with highest expression in skeletal muscle whereas LPAAT-beta was expressed predominantly in heart and liver tissues. Expression of these two cDNAs in an Escherichia coli strain with a mutated LPAAT gene (plsC) complements its growth defect and shifts the equilibrium of cellular lipid content from LPA to PA and other lipids. Overexpression of these two cDNAs in mammalian cells leads to increased LPAAT activity in cell-free extracts using an in vitro assay that measures the conversion of fluorescently labeled LPA to PA. This increase in LPAAT activity correlates with enhancement of transcription and synthesis of tumor necrosis factor-alpha and interleukin-6 from cells upon stimulation with interleukin-1beta, suggesting LPAAT overexpression may amplify cellular signaling responses from cytokines.

Acyltransferases↗

Crossing boundaries: communication between professional groups.

The NHS reforms increased emphasis on a managerial culture. In primary care this raised questions about responsibility and philosophical approaches. Greater integration between agencies brings benefits, but creates tensions. Failure to bridge the gap may result in dysfunctional teams and compromised quality of patient care. The different orientations may manifest themselves in several ways but lead to frictions that can breed hostility and prevent effective teamwork. Explores issues involving social service and community nurse teams in Dorset to identify a new framework for working, by recognizing and respecting differences and by creating a climate of dialogue. The process involves three stages. First, mutual awareness by use of meta planning which revealed several important themes, different priorities, political dynamics and organizational constraints. Second, behavioural contracting facilitated by role reversal and third, the development of consensus working protocols as a bridge for professional gaps.

Communication↗

Medicine and management: a conflict facing general practice?

Partners and practice managers are beginning to understand implications of management issues raised by recent reforms. Practices involved in this study agree the need for improvement, but partners and managers were often unable to define improvements needed. Demonstrates that effective management structure is vital to future success for general practice. To achieve this involves understanding new managerial challenges practices must meet and different organizational competences required. To change requires a radical restructure of many practice roles and several options are considered. Regardless of the chosen option the question of training remains. There is a need to involve consultants, managers, and doctors already advancing the boundaries of practice development, in a dialogue with institutions providing management training, to design suitable programmes. Academic institutions too often produce management programmes geared towards the old environment, whereas managerial skills which changes in the NHS demand from future practice managers are now required.

Budgets↗

Validation of nonradioactive chemiluminescent immunoassay methods for the analysis of thyroxine and cortisol in blood samples obtained from dogs, cats, and horses.

The performances of a radioimmunoassay method, a chemiluminescent immunoassay method, and a chemiluminescent-enzyme immunoassay method were evaluated for the analysis of cortisol and total thyroxine in blood samples obtained from dogs, cats, horses, and humans (reference samples). The analysis of cortisol in human and animal samples exhibited good precision, linearity, and recovery. The 3 methods gave comparable values for the ACTH-induced increase and the dexamethasone-induced decrease in cortisol concentrations in animal samples. The recoveries of total thyroxine from human samples, analyzed by the 3 methods, were comparable. However, the basal total thyroxine concentrations determined by the chemiluminescent immunoassay method were 30-40% lower than those determined by the radioimmunoassay and the chemiluminescent-enzyme immunoassay methods in animal samples. In both human and animal samples, the plot of thyroxine values obtained by the radioimmunoassay method against those obtained by the chemiluminescent immunoassay method or the chemiluminescent-enzyme immunoassay method was linear. However, although the slope of the radioimmunoassay versus chemiluminescent-enzyme immunoassay curve was close to unity, the slope of the radioimmunoassay versus chemiluminescent immunoassay curve was 0.6. This result suggests that, compared with the radioimmunoassay method, the chemiluminescent immunoassay method underestimated thyroxine values in animal samples but not in human samples. Although all 3 methods yielded comparable changes in thyroxine concentrations in response to thyroid stimulating hormone, they did not yield comparable thyroxine concentrations in response to T3 suppression in dogs and cats.

Adrenocorticotropic Hormone↗

List-mode likelihood.

As photon-counting imaging systems become more complex, there is a trend toward measuring more attributes of each individual event. In various imaging systems the attributes can include several position variables, time variables, and energies. If more than about four attributes are measured for each event, it is not practical to record the data in an image matrix. Instead it is more efficient to use a simple list where every attribute is stored for every event. It is the purpose of this paper to discuss the concept of likelihood for such list-mode data. We present expressions for list-mode likelihood with an arbitrary number of attributes per photon and for both preset counts and preset time. Maximization of this likelihood can lead to a practical reconstruction algorithm with list-mode data, but that aspect is covered in a separate paper [IEEE Trans. Med. Imaging (to be published)]. An expression for lesion detectability for list-mode data is also derived and compared with the corresponding expression for conventional binned data.

Image Processing, Computer-Assisted↗

Correlates of cochlear implantation, 1986-1992.

There is a paucity of information regarding the use of cochlear implants within large populations. This article describes correlates of cochlear implantation procedures using a statewide hospital discharge database. Among the 146 implant procedures, 55% involved female patients, whereas the largest groups of patients were represented by younger and older persons (27% between ages 2 and 9 years and 24% 60 years and older). A bimodal distribution was apparent for average annual age-specific rates of cochlear implantation, with the highest rates among persons aged 2 to 9 years (5.4 implants per 1 million) and persons aged 60 to 69 years (3.7 implants per 1 million). Total hospital charges, excluding professional fees, exceeded $12,000 per implant and were found to vary significantly when examined by length of stay and by calendar year of procedure. The data presented are unique with regard to the total number of cochlear implant procedures included and the large, diverse population used. This study expands knowledge concerning the epidemiology and utilization of cochlear implantation.

Adolescent↗

Mucosal permeability of ileal and colonic reservoirs for urine.

OBJECTIVES: To evaluate the intestinal mucosal permeability in continent reservoirs for urine. PATIENTS AND METHODS: The mucosal permeability in continent urinary reservoirs, constructed either from an ileal or a colonic segment (six patients each), was assessed by analysing serial samples of plasma, after instilling the reservoir with 51Cr-ethylene diaminetetra-acetic acid (51Cr-EDTA), and serum, after instillation with polyethylene glycol (PEG 400). RESULTS: There was no or negligible permeation of 51Cr-EDTA and PEG 400 in either type of reservoir, as there was no significant increase of the markers in plasma and serum, respectively. CONCLUSION: The intestinal barrier to medium-sized hydrophilic molecules seems intact in continent urinary reservoirs. The lack of significant permeation of 51Cr-EDTA confirms the usefulness of a single injection of 51Cr-EDTA for the determination of glomerular filtration rate in patients with intestinal urinary diversion.

Colon↗

Doctors and management--the development dilemma.

Identifies managerial knowledge and skills from undergraduate to medical director level and considers the development of a core management training strategy and development programme, transferable on a national basis. Reports on a questionnaire survey plus in-depth interviews with doctors and senior managers divided between grades covering hospitals, general practices and public health services. Explains that the model evolved is a synthesis of managerial models set in the context of doctors' work. Concludes that doctors agreed that more support and training from their organizations would have been useful, and that managers were generally supportive of doctors becoming involved in management, although some harboured doubts about their willingness or the effects such moves would have on established management career structures. Contends that there appears to be a 30:70 split between doctors receptive to the concept of management and those against.

Attitude of Health Personnel↗

Caudate nucleus area in drug-induced parkinsonism.

This study examined caudate nuclei areas in 10 schizophrenic subjects with and 25 schizophrenic subjects without parkinsonian symptoms. The subjects with parkinsonian symptoms were found to have statistically significantly smaller right caudate nuclei and a trend towards smaller left caudates. Cortical measurements did not differ between the groups. These results are consistent with the suggestion that antipsychotic drugs exert some neurotoxic effects, but should be viewed as preliminary and require replication.

Aged↗

Detection of Trypanosoma brucei spp. in human blood by a nonradioactive branched DNA-based technique.

We have developed a nonradioactive branched DNA (bDNA)-based assay for the diagnosis of the African trypanosomiases in simple buffy coat preparations of human blood. Two repetitive DNA sequences specific to the Trypanosoma brucei complex were chosen as targets of the bDNA assay, a technique which amplifies the signal from a target molecule rather than the target itself. Comparable sensitivities were observed with cloned target sequences, purified T. brucei DNA, procyclic trypanosomes, and bloodstream trypomastigotes. The results of bDNA analysis of human blood samples from Côte d'Ivoire (n = 50) showed excellent agreement with those of buffy coat microscopy. The bDNA technology offers certain advantages over alternative molecular biological techniques, including the simplicity of sample preparation and of the procedure itself, the stability of the reagents, the ability to process large numbers of samples simultaneously, and freedom from crosscontamination artifacts. We have successfully applied the bDNA technique to the detection of T. brucei in clinical samples from regions where T. brucei infection is endemic; to our knowledge, this is the first report of the molecular detection of T. brucei in human blood.

Animals↗

Lung function in premature rabbits treated with recombinant human surfactant protein-C.

We report the activity of recombinant human surfactant apoprotein-C (rSP-C[Cys]2) and various phospholipids in a preterm rabbit model of respiratory distress syndrome (RDS). Mixtures of rSP-C(Cys)2 and certain phospholipids had similar activity (lung compliance and lung pressure-volume behavior) to rabbit surfactant in this model. The activity of rSP-C(Cys)2 was maximal at 1 mol% protein and varied significantly with the phospholipid composition. Chemically synthesized SP-C had similar activity to rSP-C(Cys)2. Deletion of six amino-terminal residues did not affect function. Substitution of cysteines and cysteine6 with adjacent serines (rSP-C[Ser]2) by site-specific mutagenesis minimized aggregation of rSP-C but did not affect activity. Palmitoylation of cysteine5 and cysteine6 in rSP-C (rSP-C[C16]2) did not enhance the activity of rSP-C(Cys)2. We conclude that bacterial expression is a practical source of functional SP-C, and that nonacylated forms of SP-C may be useful adjuvants to phospholipids in the treatment of RDS and possibly other forms of acute lung injury.

Animals↗

Caudate nucleus morphology in tardive dyskinesia.

OBJECTIVE: The objective of this project was to test whether there are differences in the size of the caudate nucleus in schizophrenic in-patients with and without tardive dyskinesia. METHOD: The study was cross-sectional in design, examining group differences between institutionalised schizophrenic patients with and without tardive dyskinesia, using non-enhanced computerised tomography scans of the brain. The group comprised 15 schizophrenic patients with persistent tardive dyskinesia and 21 in-patient schizophrenic controls who were group-matched for demographic variables. RESULTS: The dyskinetic subjects had a significantly larger left caudate nucleus and tended to have a larger right caudate nucleus than the controls. There were no differences between the groups on any of the measures of cerebral atrophy. CONCLUSIONS: The findings can be understood within the context of models of neostriatal function. It is possible that a larger caudate nucleus could be used to identify patients at risk of developing tardive dyskinesia.

Adult↗

The signal modulator protein 14-3-3 is a target of sphingosine- or N,N-dimethylsphingosine-dependent kinase in 3T3(A31) cells.

Phosphorylation of a 28 kDa protein in 3T3(A31) cells upon addition of semi-purified kinase was induced only by sphingosine (Sph) or N,N-dimethylsphingosine (DMS), but not by 17 other lipids tested. The 28 kDa protein, a major target of Sph- or DMS-dependent kinase, is now identified as 14-3-3 protein, which modulates a number of key protein kinases involved in regulation of intracellular signaling (Aitken A, Trends Biochem Sci 20:95-97, 1995; Morrison D, Science 266:56-57, 1994). Thus, Sph and DMS modulate the function of a versatile modulator controlling a number of signaling molecules.

14-3-3 Proteins↗

Purification and cDNA cloning of a human UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase.

A UDP-GalNAc:polypeptide N-acetylgalactosaminyl-transferase (GalNAc-transferase) from human placenta was purified to apparent homogeneity using a synthetic acceptor peptide as affinity ligand. The purified GalNAc-transferase migrated as a single band with an approximate molecular weight of 52,000 by reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Based on a partial amino acid sequence, the cDNA encoding the transferase was cloned and sequenced from a cDNA library of a human cancer cell line. The cDNA sequence has a 571-amino acid coding region indicating a protein of 64.7 kDa with a type II domain structure. The deduced protein sequence showed significant similarity to a recently cloned bovine polypeptide GalNAc-transferase (Homa, F.L., Hollanders, T., Lehman, D.J., Thomsen, D.R., and Elhammer, A.P. (1993) J. Biol. Chem. 268, 12609-12616). A polymerase chain reaction construct was expressed in insect cells using a baculovirus vector. Northern analysis of eight human tissues differed clearly from that of the bovine GalNAc-transferase. Polymerase chain reaction cloning and sequencing of the human version of the bovine transferase are presented, and 98% similarity at the amino acid level was found. The data suggest that the purified human GalNAc-transferase is a novel member of a family of polypeptide GalNAc-transferases, and a nomenclature GalNAc-T1 and GalNAc-T2 is introduced to distinguish the members.

Amino Acid Sequence↗

UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase. Identification and separation of two distinct transferase activities.

Using a defined acceptor substrate peptide as an affinity chromatography ligand we have developed a purification scheme for a unique human polypeptide, UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase (GalNAc-transferase) (White, T., Bennett, E.P., Takio, K., Sørensen, T., Bonding, N., and Clausen, H. (1995) J. Biol. Chem. 270, 24156-24165). Here we report detailed studies of the acceptor substrate specificity of GalNAc-transferase purified by this scheme as well as the Gal-NAc-transferase activity, which, upon repeated affinity chromatography, evaded purification by this affinity ligand. Using a panel of acceptor peptides, a qualitative difference in specificity between these separated transferase activities in four rat organs and two human organs also revealed qualitative differences in specificity. The results support the existence of multiple Gal-NAc-transferase activities and suggest that these are differentially expressed in different organs. As the number of GalNAc-transferases existing is unknown, as is the specificity of the until now cloned and expressed GalNAc-transferases (T1 and T2), it is as yet impossible to relate the results obtained to specific enzyme proteins. The identification of acceptor peptides that can be used to discriminate GalNAc-transferase activities is an important step toward understanding the molecular basis of GalNAc O-linked glycosylation in cells and organs and in pathological conditions.

Amino Acid Sequence↗