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Biomedical subjects

J Fletcher

Publications and source records attributed to J Fletcher.

At least 235 records · Page 13Linked to original sources

Lactoferrin derived from neutrophils inhibits the mixed lymphocyte reaction.

The effects of the products of phagocytosing neutrophils on lymphocyte transcriptional activity have been investigated using allogeneic mixed lymphocyte cultures (MLC). When MLCs are grown crowded in round-bottomed wells, uptake of tritiated uridine is inhibited by the presence of neutrophil products. Similarly, inhibitory activity is shown by purified lactoferrin. The inhibitory factor released by neutrophils is positively identified as lactoferrin, since its activity is lost in the presence of specific antibody. In addition, inhibitory activity is lost when lactoferrin is removed by a monoclonal antibody (MoAb) column and is recovered with lactoferrin from the column. The active form of lactoferrin carries iron and the apoprotein is inactive. MLCs crowded in round-bottomed wells take up considerably more uridine than when spread in flat-bottomed wells, and it is this enhanced transcriptional activity that is inhibited by neutrophil-derived lactoferrin. Enhanced uridine uptake by crowded cultures is due to factors that can be transferred in the supernatants to promote uridine uptake by spread cultures. Neutrophil lactoferrin inhibits both production and effect of the transferable factor(s).

Dose-Response Relationship, Drug↗

A method for measuring rate of neutrophil phagocytosis of Staphylococcus epidermidis or Candida guilliermondii using uptake of tritiated uridine.

A method is described for measuring the rate of neutrophil phagocytosis, together with the total and intracellular kill at 20 min of 2 different organisms. The technique is sensitive over the early stages of phagocytosis as it distinguishes between adherent and engulfed organisms and is totally objective. It therefore allows detection of defects in phagocytosis which are missed if only the end point is assessed. Both total and intracellular killing are measured under the same conditions as those used to assess phagocytosis and results obtained on the same day the assay is performed.

Blood Physiological Phenomena↗

Magnetic resonance imaging of lesions of synovial origin.

Three patients with histologically differing lesions of synovial origin and two with synovial cysts, one of which was a dissecting popliteal cyst, were examined by magnetic resonance imaging (MR) and computerized tomography (CT). The three histologically proven synovial lesions were synovial sarcoma, diffuse giant cell tumor of tendon sheath, and synovial chondromatosis. In two of the five patients MR provided better anatomic and morphologic appreciation than CT, while in the others they were of equal value. CT demonstrated calcification in two of the lesions while on MR calcification could be identified in only one patient where it outlined the mass. MR did not demonstrate calcification in the substance of the diffuse giant cell tumor of tendon sheath. Coronal, transverse, and sagittal images of magnetic resonance graphically demonstrated the extent of the soft tissue masses and their relationship to bone, vessels, and soft tissue structures. Synovial sarcoma had a shorter T1 than diffuse giant cell tumor of tendon sheath (these two lesions being of comparable size) and also had a uniformly longer T2. The dissecting popliteal cyst showed the most intense signals on the T1 weighted images, while the uncomplicated synovial cyst showed a long T1. On the T2 weighted images, each type of cyst showed a long T2. The variance and overlap of intensity of MR signals suggest limited specificity in predicting the histologic nature of the synovial lesion.

Adult↗

Electrophysiological measures of regional neural interactive coupling. Linear and non-linear dependence relationships among multiple channel electroencephalographic recordings.

Linear spectral coherence (Sklar et al., 1973) measures have been used in the neurosciences to test hypotheses which address the question of whether multiple EEG recording sites are independent or whether they are activated by common sources of neurophysiological activity. This measure is appropriate when regional neural sources interact and thereby electrically activate several recording sites through linear transmission pathways which may or may not be different in their linear transformation properties. However, if the transmission media are non-linear, then interactive dependency is not necessarily revealed by a linear coherence test. Therefore, if common sources are activating EEG recording sites through nonlinear media, evaluating the resulting relationships among the signals recorded from these sites requires a test which reveals the presence of such nonlinear relationships. In neurophysiological applications, a polycoherence cross-spectral measure provides such a test for nonlinear dependency (similar to the linear coherence test) among EEG recording sites. The data requirements and statistical properties of these linear and non-linear measures are described and results of a linear coherence analysis are presented in the context of an EEG pilot study of learning-disabled children.

Biometry↗

Neutrophils are involved in the increased vascular permeability produced by activated complement in man.

To investigate the role of neutrophils in complement-induced changes in vascular permeability, skin wheal and flare responses to intradermal injection of autologous activated serum complement were measured in normal and neutropenic subjects. In normal subjects, responses were dose-dependent and were abolished by removal of C5 from serum. Biopsy of a wheal revealed neutrophils adherent to vascular endothelium. In neutropenic subjects (neutrophil count less than 0.5 X 10(9)/l), responses to complement-activated serum or a low molecular weight fraction from it were significantly reduced. This could not be accounted for by a reduction in concentration of C5 conversion products. In one subject with chronic granulomatous disease a normal response was produced. Local injection of the anti-histamine (H1) drug clemastine produced only partial inhibition of responses, while almost totally abolishing histamine-induced wheals. Systemic anti-inflammatory drugs had no effect. The data suggest that the microvascular response to activated complement in man is at least partly due to an interaction between C5 fragments and neutrophils.

Adult↗

Aspects of the neuronal and endocrine components of reflex milk ejection in conscious rabbits.

Nursing behaviour and reflex milk ejection were studied over 257 suckling periods in 26 Californian rabbits. Detailed plasma profiles of oxytocin were obtained for 161 suckling periods in 16 animals. Plasma oxytocin was detected by radioimmunoassay in serial samples of 0.2 ml blood collected during nursing. Oxytocin titres were below the lower limit of the assay (5 pmol/l) before suckling, and started to rise at a rate of 2.8 +/- 0.8 (S.D.) pmol/l per s 10-30 s after the onset of suckling. Peak levels of hormone were 345 +/- 113 pmol/l and were attained towards the end of nursing. In 33 of these experiments simultaneous records of activity from oxytocin neurones were taken whilst chronically sampling the blood. Each neurone gave an average of seven bursts of neurosecretory activity in suckling. Onset of this bursting pattern of discharge began 5-24 s before the rise in plasma oxytocin was detected. Oxytocin neurone activity alone was monitored in a further 55 suckling periods in eight rabbits. A marked relationship between the duration of suckling period, milk yield, peak oxytocin levels and the length of neurosecretory bursts was demonstrated over the course of lactation. All four parameters increased in parallel from day 1 to reach maximal values on days 15-20 of lactation then started to wane until the doe ceased nursing her litter on days 25-27 of lactation.

Animals↗

The role of lactoferrin released by phagocytosing neutrophils in the regulation of colony-stimulating activity production by human mononuclear cells.

There remains a controversy about the alleged inhibitory effect of lactoferrin on production of colony-stimulating activity (C.S.A.) by mononuclear cells. We confirm the inhibitory action of both lactoferrin purified from human breast milk and that released from phagocytosing neutrophils. To show the inhibitory effect, it is necessary to plot the dose-response curve of medium conditioned by mononuclear cells with and without lactoferrin. Crowding cells to promote contact is essential for the fraction of C.S.A. production inhibitable by lactoferrin. Saturation of purified lactoferrin by addition of iron salts in vitro may introduce an artifact, as this lactoferrin retained its inhibitory activity at much greater dilutions than lactoferrin released from phagocytosing neutrophils.

Colony-Stimulating Factors↗

Evaluation of school performance: dyslexia and attention deficit disorder.

The primary focus of the diagnostic evaluation is to determine whether the child's problems fit the criteria for a diagnostic entity. In the case of school problems, the two most common disorders to be considered are learning disability and attention deficit disorder. Historical information from parents and teachers together with psychometric data are at the core of the assessment process. Helpful insights may be gathered from the neuromaturational examination while specific laboratory measures including electrophysiological, neurochemical, neuroradiological and psychophysiological have not been shown to be helpful in distinguishing either learning disability or attention deficit disorder. The physician is urged to take a more active role in the psychometric component of the examination. Inquiry should be made about the reliability and validity of instruments used before accepting any recommendations based on a particular test. Care should also be taken to insure that the tests used in the formulation have been individually administered and that the child's performance is noted in untimed as well as timed circumstances. While a comprehensive evaluation should inquire into social, familial and medical etiologies, this should be accomplished with the knowledge that except for family history, there may be no other contributing factors that emerge. Learning disability and attention deficit disorder are high prevalence disorders. Time and energy should not be expended in searching for rare events to invoke as an explanation for these frequent occurrences.

Attention Deficit Disorder with Hyperactivity↗

Relation of gene expression (allotypes) of the fourth component of complement to insulin dependent diabetes and its microangiopathic complications.

About a quarter of insulin dependent diabetics have low concentrations of the fourth component of complement (C4), and a low concentration of C4 is associated with diabetic microangiopathy. The variability of the expression of the C4 gene was compared in insulin dependent diabetics with and without microangiopathy and controls. Of the two genes coding for C4, the A gene (C4A) was not expressed--that is, C4A null--in 16 (13%) of the 126 insulin dependent diabetics compared with none of the 93 controls (p less than 0.001), and all these 16 subjects had low concentrations of C4. Lack of expression of the other C4 gene (C4B) was not associated with insulin dependent diabetes, but a rare variant, C4B3, was significantly increased in the diabetics (21/126; 17%) compared with the controls (none) (p less than 0.001). The prevalence of C4B3 was also increased in the diabetics with complications when compared with those without (14/50 (28%) v 7/76 (9%), p less than 0.01). Low plasma C4 concentrations in insulin dependent diabetics are at least partly due to variation in the expression of the C4 gene. The association of the rare C4B3 variant with microangiopathy suggests a genetic component of its aetiology.

Adolescent↗

Experimentally produced synovial sarcoma in mice.

BALB/c and C57 B1/6 mice which received weekly subcutaneous injections of a cannabinoid developed tumors at the points of injection. In the groin the tumors were fibrosarcomas, while in the interscapular region they were anaplastic sarcomas and synovial sarcomas. The latter developed faster and were larger in cannabinol - and cannabidiol-treated C57 B1/6 mice than in delta 9-tetrahydrocannabinol-treated BALB/c mice. This difference could not be attributed to strain differences. 2 cannabidiol- and 1 cannabinol-treated C57 B1/6 females with the fastest growing synovial sarcomas were pregnant and, in addition, 2 of them developed mammary adenocarcinomas, indicating that they were rich in estrogen. On the other hand, it is known that delta 9-tetrahydrocannabinol causes a decrease in the sex hormone. It is consequently thought that the cannabinoids are only initiators of synovial sarcoma, while growth or promotion of the latter is influenced partially or entirely by the sex hormone.

Adrenal Gland Neoplasms↗