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Biomedical subjects

R Turner

Publications and source records attributed to R Turner.

At least 217 records · Page 12Linked to original sources

Propeptide recognition by the vitamin K-dependent carboxylase in early processing of prothrombin and factor X.

Precursors of vitamin K-dependent proteins are synthesized with a propeptide that is believed to target these proteins for gamma-carboxylation by the vitamin K-dependent carboxylase. In this study synthetic propeptides were used to investigate gamma-carboxylation of the prothrombin and factor X precursors in rat liver microsomes. The extent of prothrombin processing by the carboxylase was also investigated. Antisera raised against the human prothrombin and factor X propeptides only recognized precursors with the respective propeptide regions. The data demonstrate structural differences in the propeptide region of the prothrombin and the factor X carboxylase substrates which raises questions about the hypothesis of a common propeptide binding site on the carboxylase for all precursors of vitamin K-dependent proteins. The hypothesis of separate binding sites is supported by data which demonstrate differences in binding of the prothrombin and factor X precursors to membrane fragments from rough and smooth microsomes. gamma-Carboxylation of the prothrombin precursors in vitro was investigated with conformational specific antibodies raised against a portion of the Gla (gamma-carboxyglutamic acid) region extending from residue 15 to 24. The synthetic peptide used as antigen contains three of the ten potential Gla sites in prothrombin. It is shown that these antibodies do not recognize mature prothrombin but recognize the decarboxylated protein. It is also demonstrated that the epitope is Ca2(+)-dependent. The antibodies were used to assess gamma-carboxylation of the prothrombin precursor in membrane fragments from microsomal membranes. The results suggest that microsomal gamma-carboxylation does not involve Glu residues 16, 19 and 20 of the Gla region.

Amino Acid Sequence↗

Echo-planar imaging with asymmetric gradient modulation and inner-volume excitation.

Single-shot echo-planar imaging is notoriously vulnerable to image artifacts, arising from the necessity of alternate echo time reversal during image reconstruction and from static field inhomogeneity. A technique for overcoming these problems, which further permits imaging on systems with relatively poor gradient waveforms, when data are collected always with the same gradient polarity, is presented. Subsectional and 3D volume imaging are presented as well as a novel phase-correction method for Hermitian symmetry in "half-Fourier" echo-planar imaging.

Humans↗

Single-shot localized echo-planar imaging (STEAM-EPI) at 4.7 tesla.

The resolution and homogeneity limitations of echo-planar imaging (EPI) are overcome by zoom imaging of an easily shimmed localized volume. Use of the stimulated echo enables single-shot localization. In vivo 0.5-mm resolution EPI images of selected regions of a cat brain at 4.7 T are presented.

Animals↗

Quality of life in non-insulin-dependent diabetes and a comparison with insulin-dependent diabetes.

The reported effects of diabetes on quality of life have been assessed in two groups of attenders at out-patient clinics: 1. One hundred and twenty-one non-insulin-dependent diabetic patients randomly allocated to diet, tablet or ultralente insulin therapy; 2. Fifty-seven patients with insulin-dependent diabetes consecutively attending an out-patient clinic. The overall picture for those with non-insulin-dependent diabetes was of relatively little disruption to most areas of life, but 27% reported considerable loss of enjoyment and reduction in social life. High fasting plasma glucose was significantly associated with fatigue and leisure difficulties. The type of therapy, tablet, diet or insulin, made little difference to psychological, social or attitude variables. Those with insulin dependent diabetes showed similar psychological morbidity, but described a rather different pattern of social consequences with more effects on work and less on leisure.

Activities of Daily Living↗

Methylprednisolone acetate does not cause inflammatory changes in the epidural space.

Few studies have examined the possible adverse effects that epidural injection of depot corticosteroid preparations may have on meningeal membranes and nervous tissue. Thirty-six healthy adult white rabbits received 0.3 ml/kg epidural injections of either lactated Ringer's solution (negative control group), 1% lidocaine containing methylprednisolone acetate (study group), or normal saline containing talc (positive control group). Animals were killed either 4 or 10 days after injection and stained sections of the spinal cord and meningeal membranes were examined by light microscopy. In all animals that received either lactated Ringer's solution or lidocaine with methylprednisolone acetate, microscopic examination of specimens taken from the L5-L6 interspace revealed no white cell infiltrates and no fibroblastic activity. All animals that received epidural injections of normal saline containing talc had marked infiltration of tissue macrophages in the epidural space. There was no thickening of the meningeal membranes or nerve roots in any animal. The complete lack of inflammatory changes and meningeal thickening demonstrated in this pilot study helps to confirm the safety of methylprednisolone acetate when injected into the epidural space.

Animals↗

Echo-planar imaging of intravoxel incoherent motion.

The recently established single-shot technique of echo-planar imaging of intravoxel incoherent motion (IVIM) for determining and imaging the variations of microscopic motions of water has been applied to studies of water perfusion in phantoms and to in vivo studies of diffusion and perfusion in cat and human brains. The phantom results demonstrate that perfusion levels comparable with those found in vivo have easily observable and reproducible effects on signal amplitude that are consistent with previous IVIM theory. Reliable measurements of the diffusion coefficient in various types of brain tissue have been obtained. The results for white matter are consistent with the existence of anisotropic diffusion in oriented bundles of myelinated nerve fibers. The results for gray matter can be fitted to the IVIM theory and suggest a value of up to 14% for the fraction of the signal contributed by randomly perfusing fluid in normal cerebral cortex.

Animals↗

Ethylene: receptors and action.

The characterisation and purification of the ethylene binding protein from developing cotyledons of Phaseolus vulgaris is described. Polyclonal antibodies to this protein recognise homologous proteins in peas, tomatoes and Arabidopsis. Direct binding assays and results from immunological studies indicate that more binding protein is present in abscission zones of Phaseolus than in petioles; ethylene treatment increases binding site abundance in abscission zones. Binding sites for ethylene in peas. Arabidopsis and rice are described indicating that there exist two classes differing only in their rate constants of association and dissociation. Arabidopsis mutants wholly insensitive to ethylene may be receptor deficient and their possible use in receptor studies is assessed. It is proposed that those binding sites with high rate constants of association are functional receptors. The sites with low rate constants of association may be receptors but may also represent receptor precursors or internalised receptors.

Antibodies↗

Integrated hospital and community psychiatric services and use of inpatient beds.

The impact of introducing a divisional psychiatric service based in the community in Nottingham in 1981 on adult psychiatric admissions (patients aged 15-65) was examined with data from the Nottingham case register. During 1980-5 the number of psychiatric admissions fell significantly (4.5% a year) compared with the national figures (0.46% a year). Admissions were reduced most for the diagnoses of affective psychosis and neurotic and personality disorders. The average duration of admission fell by 3.6% a year, and use of inpatient beds fell by 37.5%. Integrating hospital and community psychiatric services by creating sectors is a viable and economically feasible way of improving psychiatric services.

Adolescent↗

Leucine repeats and an adjacent DNA binding domain mediate the formation of functional cFos-cJun heterodimers.

The discovery that the AP-1 family of enhancer binding factors includes a complex of the cellular Fos (cFos) and cellular Jun (cJun) proteins established a direct and important link between oncogenesis and transcriptional regulation. Homodimeric cJun protein synthesized in vitro is capable of binding selectively to AP-1 recognition sites, whereas the cFos polypeptide is not. When cotranslated, the cFos and cJun proteins can form a stable, heterodimeric complex with the DNA binding properties of AP-1/cJun. The related proteins Jun B and vJun are also able to form DNA binding complexes with cFos. Directed mutagenesis of the cFos protein reveals that a leucine repeat structure is required for binding to cJun, in a manner consistent with the proposed function of the "leucine zipper." A novel domain adjacent to, but distinct from, the leucine repeat of cFos is required for DNA binding by cFos-cJun heterodimers. Thus experimental evidence is presented that leucine repeats can mediate complex formation between heterologous proteins and that promotes further understanding of the molecular mechanisms underlying the function of two proto-oncogene products.

Amino Acid Sequence↗

Snapshot imaging at 0.5 T using echo-planar techniques.

Echo-planar imaging using a magnetic field strength of 0.5 T has resulted in an improvement in image quality compared with recent images published at 0.1 T. The sensitivity of the technique to main magnetic field inhomogeneity and transient eddy currents has necessitated innovations in gradient and radiofrequency coil design. These improvements are described, and new variations in the echo-planar pulse sequence which provide better contrast and allow separate imaging of water and fat distributions are presented.

Abdomen↗

Effects of intravoxel incoherent motions (IVIM) in steady-state free precession (SSFP) imaging: application to molecular diffusion imaging.

A theoretical analysis of the effects of diffusion and perfusion in steady-state free precession (SSFP) imaging sequences sensitized to intravoxel incoherent motions by magnetic field gradients is presented and supported by phantom studies. The capability of such sequences to image diffusion and perfusion quickly was recently demonstrated. The possible residual effects of T1 and T2 in diffusion measurements are evaluated, as are the effects of the sequence design and the acquisition parameters (repetition time, flip angle, gradient pulses). It is shown theoretically and confirmed by experiments on phantoms that diffusion coefficients can be directly measured from SSFP images when large enough diffusion gradient pulses are used.

Diffusion↗

Attenuation of spontaneous, nocturnal growth hormone secretion in children with hypothyroidism and its correlation with plasma insulin-like growth factor I concentrations.

To define further the alterations in growth hormone (GH) secretion that occur in childhood hypothyroidism, we quantified spontaneous nocturnal secretion in seven patients with primary hypothyroidism. We examined the relationship between plasma insulin-like growth factor I (IGF-I) and GH secretory profile in each patient before and during therapy with L-thyroxine. In contrast to the results of previous studies that used pharmacologic tests of GH release, spontaneous GH secretion was consistently attenuated in the hypothyroid state. Mean nocturnal GH levels were reduced by 58% (1.48 +/- 0.38 ng/ml, mean +/- SEM) in comparison with values obtained during L-thyroxine therapy (3.54 +/- 0.71 ng/ml, p less than 0.01). Coincident with the reduced levels of GH, plasma IGF-I concentrations were lower in patients before therapy (0.46 +/- 0.20 U/ml) compared with concentrations during therapy (1.50 +/- 0.34 U/ml, p less than 0.01). In treated, euthyroid patients, GH and IGF-I levels were equivalent to those of normal children. The excellent correlation (r = 0.77) between plasma IGF-I and mean nocturnal GH concentrations indicates that reduced plasma IGF-I levels in hypothyroidism probably result from suppressed GH secretion.

Adolescent↗

Whole-body echo-planar MR imaging at 0.5 T.

The ultra-high-speed echo-planar imaging technique produces instant snapshot magnetic resonance images in exposure times ranging from approximately 10 to 100 msec. A particular variant, the modulus blipped echo-planar single-pulse technique (MBEST), possesses two advantages: First, it makes the technique experimentally more robust; second, it introduces inherent T2 weighting in the images. The authors have used MBEST with an exposure time of 64 msec to explore the potential range of clinical applications in a series of normal volunteers. Applications include evaluation of the heart, renal function, and gastrointestinal tract. All images were obtained with proton resonances at 22 MHz.

Abdomen↗