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Biomedical subjects

B Chapman

Publications and source records attributed to B Chapman.

At least 91 records · Page 5Linked to original sources

Expression of a cytomegalovirus IE-1-factor VIII cDNA hybrid gene in transgenic mice.

A construct containing the 5' end of the human cytomegalovirus major immediate early gene fused to the human coagulation factor VIII cDNA was used to produce transgenic mice. Two out of five transgenic lines transcribed the construct. The expression was consistently seen in a limited number of tissues and was highest in muscle tissues. This is in contrast to the almost ubiquitous activity demonstrated in earlier studies with the IE-1 enhancer/promoter. Human factor VIII protein was detected immunochemically in muscle tissues at levels several times higher than in human plasma.

Animals↗

Diencephalic idiopathic gliosis: an unusual hypothalamic syndrome of dermopathy, diarrhea and growth arrest.

This case report of a 16-year-old girl describes the association of chronic diarrhea and lower limb dermopathy with an unusual and widespread gliosis within hypothalamic and other diencephalic structures. This syndrome to our knowledge has not been previously reported. Hypothalamic disease was suggested during life by examination findings of sustained hypothermia, altered sleep-wake cycles and abnormal cortisol diurnal rhythms. Profound growth arrest from the age of 8 yr (growth velocity < 1.4cm/yr) despite normal levels of growth hormone and response to physiological stimuli were additional unusual features. Autopsy after sudden death at 16 yr showed extensive gliosis in hypothalamic and adjacent diencephalic structures with proportionately little neuronal loss--suggesting an unidentified stimulus to glial proliferation. In the absence of evidence of other organ dysfunction it is suggested that dermopathy and chronic diarrhea in this case may have an autonomic basis. The impaired tissue response to growth hormone could be due to chronic hypothermia or involvement of some other (unidentified) hypothalamic factor regulating growth velocity.

Adolescent↗

Origin of orientation tuning in the visual cortex.

The results of recent experiments have thrown new light on the neuronal connections underlying orientation-selective responses in the primary visual cortex of adult animals. The pattern of afferent input from the lateral geniculate nucleus to the cortex appears to be specific for orientation, while intracortical inhibitory connections appear to be non-specific in this respect. Experimental and theoretical studies have suggested that the development of cortical cell orientation tuning is an activity-dependent process.

Animals↗

Induction of specific storage organelles by von Willebrand factor propolypeptide.

Endothelial cells store the multimeric adhesive glycoprotein von Willebrand factor (vWf), which promotes the formation of a platelet plug at the site of vessel injury. To investigate the packaging of vWf into the granules called Weibel-Palade bodies, we expressed pro-vWf cDNA and cDNA lacking the prosequence in a variety of cell lines. Storage granules formed only in cells that contain a regulated pathway of secretion. Furthermore, packaging required the prosequence. Pro-vWf, lacking the C-terminal region involved in interchain disulfide bonding, formed granules. We conclude that the signal for storage is universal in that an adhesive glycoprotein can be stored by a hormone-secreting cell; the storage of vWf is independent of its covalent multimeric structure; the unusual rod shape of Weibel-Palade bodies is due to vWf; and the vWf propolypeptide is necessary for the formation of vWf storage granules.

Animals↗

Neutrophil activation by Helicobacter pylori.

Helicobacter pylori infection of the stomach is accompanied by a persistent polymorphonuclear leukocyte (PMNL) infiltrate of the mucosa. The aim of this work was to study the activation of human PMNL by substances produced by H pylori. Filtered H pylori conditioned media stimulated a significant PMNL oxidative burst (p less than 0.002). This was equal to 26% of the maximal response stimulated by the PMNL chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP, 1 mumol/l). The response to FMLP was prolonged by the combined presence of complement inactivated human anti-H pylori plasma and conditioned medium (p less than 0.002). High pressure liquid chromatography of an extract of conditioned medium showed a fraction that stimulated PMNL, eluted, and antigenically cross reacted with FMLP. Washed H pylori cells, and those opsonised with complement inactivated human anti-H pylori plasma, did not induce a significant oxidative burst. Opsonized H pylori, however, prolonged the oxidative burst induced by FMLP (p less than 0.02). In conclusion, H pylori synthesizes and secretes a substance, probably FMLP, that may account for the PMNL accumulation that accompanies H pylori infections. Immune complexes composed of H pylori antigen and specific antibody potentiate the PMNL oxidative burst. This combination of H pylori derived products, and host PMNL and antibodies, may be involved in the mucosal damage observed in H pylori associated gastritis.

Antibodies, Bacterial↗

Relation of cortical cell orientation selectivity to alignment of receptive fields of the geniculocortical afferents that arborize within a single orientation column in ferret visual cortex.

Neurons in the primary visual cortex of higher mammals are arranged in columns, and the neurons in each column respond best to light-dark borders of particular orientations. The basis of cortical cell orientation selectivity is not known. One possible mechanism would be for cortical cells to receive input from several lateral geniculate nucleus (LGN) neurons with receptive fields that are aligned in the visual field (Hubel and Wiesel, 1962). We have investigated the relationship between the arrangement of the receptive fields of geniculocortical afferents and the orientation preferences of cortical cells in the orientation columns to which the afferents provide visual input. Radial microelectrode penetrations were made into primary visual cortex of anesthetized adult sable ferrets. Cortical cells were recorded throughout the depth of the cortex, and their orientation preferences were determined. Cortical cell responses were then eliminated by superfusion of the cortex with either kainic acid (Zahs and Stryker, 1988) or muscimol. After the drug treatment, responses from many single units with distinct receptive fields were recorded. These responses were presumed to be those of geniculocortical afferents, because they had the response properties characteristic of LGN neurons, and because they could be recorded only in cortical layers that receive geniculate input. In 16 of 18 cases, the afferent receptive fields recorded in a single penetration covered an elongated region of visual space. In these penetrations, the best-fit line through the centers of the afferent receptive fields generally paralleled the preferred orientation of cortical cells recorded at the same site in cortex. These results are consistent with the Hubel and Wiesel (1962) model for the construction of oriented visual cortical receptive fields from geniculate inputs with aligned receptive fields.

Afferent Pathways↗

Echo-planar imaging of the human fetus in utero.

We have demonstrated that echo-planar imaging can be used to produce high-quality snapshot images of the human fetus in utero in a fraction of a second. These images are free of motional artifact or blurring and allow detailed depiction of fetal structures in normal and pathological pregnancies.

Fetal Heart↗

High-speed multislice T1 mapping using inversion-recovery echo-planar imaging.

Tissue contrast in MR images is a strong function of spin-lattice (T1) and spin-spin (T2) relaxation times. However, the T1 relaxation time is rarely quantified because of the long scan time required to produce an accurate T1 map of the subject. In a standard 2D FT technique, this procedure may take up to 30 min. Modifications of the echo-planar imaging (EPI) technique which incorporate the principle of inversion recovery (IR) enable multislice T1 maps to be produced in total scan times varying from a few seconds up to a minute. Using IR-EPI, rapid quantification of T1 values may thus lead to better discrimination between tissue types in an acceptable scan time.

Fourier Analysis↗

Echo planar imaging of an infant with pectus excavatum.

Echo planar imaging has enabled us to image safely and without sedation the thorax of an infant with pectus excavatum deformity. The heart was displaced into the left side of the thorax, and the right lung was calculated to be 1.6 times larger than the left lung.

Funnel Chest↗

Study of internal structure of the human fetus in utero by echo-planar magnetic resonance imaging.

The ultrafast echo-planar magnetic resonance imaging technology, developed and built in Nottingham, has been used to produce the first snapshot images of the human fetus in utero. The imager, operating at a proton resonance frequency of 22 MHz, produces transaxial views in 64 or 128 milliseconds. These images comprise either 64 x 128 or 128 x 128 pixels with an in-plane resolution of 3 x 3 mm2. The slice thickness is 10 mm. Fetal scans of up to 32 contiguous slices are produced in a few minutes. These have been used to study the internal structure of the uterus and the fetus in a range of cases with gestations ranging from 26 weeks to term. Echo-planar imaging seems particularly suitable as an imaging modality since its high speed obviates image blurring arising from fetal motion.

Fetal Diseases↗

Estimation of lung volume in infants by echo planar imaging and total body plethysmography.

Echo planar imaging (an extremely fast method of magnetic resonance imaging) was used to measure lung volume in a group of nine infants, all of whom had had respiratory problems. The mean echo planar imaging estimate of total lung volume was 44 +/- 9 ml/kg. In each case the right lung was larger than the left (ratio 52.8:47.2%). The mean thoracic gas volume was 36 +/- 8 ml/kg. The entire sequence of images of the thorax (about 400) takes five minutes to complete, infants require no sedation, and there are no side effects.

Female↗

Non-isotopic, two-step free thyroxine immunoassay: a better measure of free thyroxine than analogue radioimmunoassay.

Plasma or serum free thyroxine (T4) was measured by a novel non-isotopic, two-step immunoassay in 373 consecutive patients attending a thyroid clinic, in whom thyroid status was categorized according to clinical findings, supported by routine thyroid function tests. The 95% confidence limit of free T4 in the euthyroid patients (n = 112) was 7-20 pmol/L. Free T4 concentrations within the reference range were found in six of 40 patients with primary hypothyroidism and nine of 182 patients with overt thyrotoxicosis, six of whom had T3 toxicosis. Serum or plasma free T4 measured by the two-step method showed improved diagnostic specificity over an analogue RIA in selected groups of euthyroid patients in whom abnormal binding of analogue T4 can affect the validity of the result. Free T4 results found by analogue RIA and the two-step method in 58 patients who were receiving thyroxine replacement therapy were similar. The between-assay precision of the two-step method was poor ranging from a coefficient of variation of 9.7% to 19.3% over a free T4 concentration range of 5.0 to 46.0 pmol/L. We conclude that the two-step methodology offers diagnostic advantages for a laboratory which receives specimens from such patients for exclusion of thyroid disease but that improved assay precision is required before it could be used in a routine situation.

Autoantibodies↗

Echo planar imaging of the human fetus in utero at 0.5 T.

The snap-shot capability of the echo-planar imaging technique is used to freeze motion effectively in human fetal studies in utero. These first results obtained at 0.5 T demonstrate diagnostic quality images without the need for averaging. Although averaging improves the image signal to noise ratio, it is shown that significant image blurring is produced even when only eight separate images are averaged over a period of a few seconds. Results are presented showing anatomical detail of the internal organs of the fetus. Some pathology is also demonstrated. These results were obtained using the modulus blipped echo-planar single-pulse technique (MBEST). Running at 10 frames/second, the modulus version of the fast low-angle excitation echo-planar technique (FLEET) is used to produce ungated fetal cardiac movies.

Female↗

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↗

PEEP--a rapid chemical-shift imaging method.

The phase-encoded echo-planar (PEEP) technique, a variant of echo-planar imaging, is used to achieve simultaneous high-speed spatial and chemical-shift data acquisition. This technique is the 2DFT equivalent of the projection reconstruction echo-planar method for chemical-shift imaging. Examples of images and spectra obtained using the PEEP method are presented.

Magnetic Resonance Imaging↗