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Biomedical subjects

J Sheldon

Publications and source records attributed to J Sheldon.

At least 19 recordsLinked to original sources

Neuroanatomic differences between dyslexic and normal readers on magnetic resonance imaging scans.

The areas of six bilateral brain segments in the right and left hemispheres, on a horizontal brain section, and the area of subdivisions of the corpus callosum, on a midsagittal brain section, were measured on magnetic resonance images obtained from 21 dyslexic and 29 control subjects. In the entire group, the frontal half of the horizontal brain section showed asymmetry, with the right side being larger, whereas posteriorly only the occipital polar segment was asymmetrical, with the left side being larger. Dyslexic subjects exhibited asymmetry, with the right side greater than the left side, in contrast to the relatively symmetrical pattern that is normally observed in the midposterior segment that corresponds to the angular gyrus. In the corpus callosum, dyslexic subjects were found to have a larger splenium than nondyslexic subjects, and dyslexic female subjects were found to have a larger splenium than dyslexic male subjects. Because transcallosal pathways connecting the left and right angular gyrus regions traverse through the splenium of the corpus callosum, the above findings in dyslexic subjects suggest an anatomic abnormality in the angular gyrus region.

Adult

Cytokine induction of neopterin production.

The pteridine neopterin is a marker of immunological activation and has been shown to be a useful marker of graft-versus-host disease (GVHD) in bone marrow transplant patients. High levels of both neopterin and interferon-gamma (IFN-gamma) were produced in vitro during mixed lymphocyte responses, which may be considered to be a model of the primary events leading to GVHD. Neopterin was shown to be produced by monocytes in response to stimulation with IFN-gamma, but not other cytokines. However, the interleukins IL-1 alpha, IL-1 beta, IL-2, and tumour necrosis factor (TNF) alpha and beta, but not IL-6, stimulated neopterin production by unfractionated peripheral blood mononuclear cells (PBMC), and culture supernatants from PBMC stimulated with IL-1 alpha, IL-1 beta, IL-2 and IL-6, but not TNF-alpha or TNF-beta induced neopterin production following transfer to fresh monocyte cultures. It therefore appears that cytokines may generate neopterin by induction of IFN-gamma, by synergy with low levels of induced IFN-gamma, or by non-IFN-gamma-dependent mechanisms.

Biopterins

Overestimation of monoclonal immunoglobulin by immunochemical methods.

A comparison of paraprotein estimation by scanning densitometry with corresponding immunoglobulin concentration measured by rate immunonephelometry, fixed-time immunonephelometry and kinetic immunoturbidimetry using a large number of sera has indicated overestimation of the immunoglobulin by liquid phase immunoassays in the presence of a monoclonal component. The effect was seen with all three major immunoglobulin isotypes but was most marked with IgM paraproteins when measured by kinetic nephelometry. The overestimations could not be explained by presence of rheumatoid factors or immune complexes in the serum samples, or by non-parallelism, over a range of dilutions, of the reaction of sample and calibrant with the antiserum. The source and species of antiserum used was a major contributory factor.

Antibodies, Monoclonal

C-reactive protein as a diagnostic test of sepsis in the critically ill.

Changes in the plasma concentration of C-reactive protein were assessed as a diagnostic test for sepsis in critically ill patients. Forty-nine episodes of secondary sepsis were identified in 31 patients. In 43 out of the 49 episodes there was a 25% or greater change in the concentration of C-reactive protein on the day that sepsis was diagnosed but in six episodes of sepsis the change was less than 25%. A 25% rise in the plasma concentration of C-reactive protein in the absence of other non-infective causes of a raised C-reactive protein, such as inflammation, tissue injury or surgery, is highly suggestive of infection, but failure of the C-reactive protein to rise does not eliminate a diagnosis of sepsis.

Bacterial Infections

Plasma neopterin as an adjunct to C-reactive protein in assessment of infection.

C-reactive protein (CRP) concentrations are increased in plasma in people with inflammatory conditions and bacterial infections. Plasma neopterin concentrations are increased in people with bacterial septicemias, viral infections, and graft vs host disease. Plasma concentrations of CRP and neopterin were measured daily in 21 bone-marrow transplant (BMT) patients, 64 patients in intensive-care units (ICU), and 12 patients with squamous cell carcinoma of the head and neck (HN). In the BMT patients, plasma neopterin measurements in addition to CRP measurements allowed infectious episodes to be distinguished from graft vs host disease. In the ICU patients, increased concentrations of CRP were not specific for infection and the additional plasma neopterin measurements did not improve this specificity. In all three patient groups, the derivation of a neopterin/CRP ratio was of no clinical use. These three groups of patients showed patterns of CRP and neopterin concentrations characteristic of their underlying diseases, the BMT patients with the immunological activation of graft vs host disease showed predominantly increased concentrations of plasma neopterin, ICU patients with infectious and inflammatory conditions had increased concentrations of both CRP and neopterin in plasma, and the HN group with localized inflammation showed increased plasma concentrations of CRP without increases in neopterin.

Adolescent

Metabolic asymmetries in asymptomatic HIV-1 seropositive subjects: relationship to disease onset and MRI findings.

Fifteen male homosexual subjects (mean age 31.6 +/- 7.2 yr) who were asymptomatic, but HIV-1 seropositive (HIV+) were compared to 15 male age-matched HIV-1 seronegative (HIV-) subjects using resting PET/FDG studies and MR scans. Mean cerebral metabolic rates for glucose (mg/100 g/min) in the HIV+ and HIV- subjects were 7.7 +/- 1.7 and 7.0 +/- 2.1, (p = 0.44), respectively. An index of regional metabolic asymmetry for the whole brain was 5.8% +/- 3.2% in the HIV+ and 2.7% +/- 2.3% in the HIV- (p = 0.002), and the difference was most prominent in the prefrontal area. Significant asymmetries were found in 10/15 HIV+ subjects, primarily in prefrontal (7/15) and premotor (4/15) regions. MRI scans showed no abnormalities on clinical or quantitative evaluation in HIV+ subjects. Upon follow-up of HIV+ subjects over 18-40 mo, seven became symptomatic, of which two died. There was no relationship between the presence of PET scan abnormalities and earlier onset of symptomatic disease.

Adult

Localization of peripheral cholecystokinin receptors in vivo using the cholecystokinin antagonist [3H](+/-)-MK-329.

Cholecystokinin (CCK) regulates various gastrointestinal functions through specific receptors. The mechanisms responsible for disorders of these functions could be elucidated by non-invasively localizing CCK receptors and quantifying their number in vivo. MK-329 is a highly selective and very high affinity antagonist at the peripheral CCK receptor. We investigated the in vivo binding of [3H](+/-)-MK-329 in mice to determine if binding to CCK receptors could be detected after systemic administration of the tracer. The uptake of [3H](+/-)-MK-329 increased in the pancreas from 5 min to 4 h after administration. The binding was saturable, stereospecific, and more than 80% specific. A total/non-specific binding ratio of 43 was reached at 8 h post-injection. The pancreas was the only organ where specific binding could be detected. Our results suggest that MK-329 labeled with a positron emitter such as C-11 could be used with positron emission tomography to image and quantify peripheral CCK receptors in man.

Animals

An investigation of immunological subclass function in burned adults.

The serum concentrations of the immunoglobulin subclasses and their functional activity against pneumococcal polysaccharide (PPS) and E. coli antigens have been studied for 15 days in 12 adult burned patients, of whom six were randomly allocated to receive biosynthetic human growth hormone (somatropin) and six to form a control group. The concentrations of the major subclasses, IgG1 and IgG2, fell below their normal ranges as a result of injury by burning but had recovered significantly by the eleventh day of the study. There were no significant changes in the concentrations of the IgG3 and IgG4 subclasses, however, the relative proportions of the four subclasses remained unchanged and were comparable to those found in normal man. Significantly reduced functional activities, compared with normal volunteers, were observed in all the subclasses except IgG1. The activities of the major subclasses during the study were correlated with their serum concentrations and when corrected for their concentrations were comparable to those of normal blood donors. There were no significant increases in concentrations or activity of the subclasses as a result of somatropin administration. It is concluded that patients with moderately sized burns have reduced immunoglobulin function which results from the changes in serum concentration rather than from any qualitative change and that somatropin administration results in no improvement in immunoglobulin function.

Adolescent

MR signal abnormalities in memory disorder and dementia.

MR imaging of the brain, performed in 86 normal subjects and 113 patients with objective memory disorder or dementia, demonstrated white- and gray-matter areas of high signal intensity on long TR images (short and long TE). Hyperintensities were analyzed with respect to size (on a scale of 0-3) and location: lesions were periventricular, subcortical, or cortical. The patients with memory disorder and dementia were categorized as having probable/possible Alzheimer disease, a combination of Alzheimer disease and multiinfarct cognitive disorder, or multiinfarct cognitive disorder alone on the basis of clinically determined Hachinski ischemic scores. Significant correlations were found between age and scores for periventricular lesions (r = .40, p less than .0005) and subcortical lesions (r = .39, p less than .0005) in normal subjects. Correlations were also found between the Hachinski ischemic score and scores for periventricular lesions (r = .21, p less than .01), subcortical lesions (r = .27, p less than .0002), and cortical lesions (r = .32, p less than .0005) in subjects with memory disorder/dementia. Comparing multiinfarct cognitive disorder, Alzheimer disease, and normal groups, the mean scores for periventricular lesions were 12.0 +/- 4.6, 7.6 +/- 4.8, and 3.4 +/- 2.6, while mean scores for subcortical lesions were 10.8 +/- 12.2, 4.1 +/- 6.4, and 0.8 +/- 1.2, respectively. Periventricular lesions were present in 99-100% of patients with Alzheimer disease and multiinfarct cognitive disorder. On the other hand, subcortical lesions, which were identified in 100% of patients with multiinfarct cognitive disorder, were present in only about half of the patients with Alzheimer disease. Thus, scores for both periventricular and subcortical lesions are positively correlated with age and risk factors for cerebrovascular disease and also are significantly increased in the presence of objective memory disorder or dementia. These results imply that in the subject groups considered here, elderly patients with vascular dementia are most likely to have severe white-matter abnormalities on MR scans. The score for subcortical lesions appears to be more helpful than the score for periventricular lesions in distinguishing vascular dementia from Alzheimer disease and normal aging, so that a patient with prominent subcortical white-matter abnormalities is more likely to have a diagnosis of vascular than degenerative dementia.

Adult

Diabetic coma.

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Adolescent

Secretory capacity and ultrastructure of rat pancreatic islets after preservation of pancreas in different conditions.

Experiments were performed with rat pancreas to investigate optimum conditions for obtaining and preserving the pancreas for subsequent isolation of islets that were viable by both functional and morphological criteria. After only 30 min of warm ischaemia, the yield and viability of islets that could be isolated were poor. However, if the pancreas was removed and placed immediately in a cold bicarbonate-buffered medium, which was supplemented with HEPES to maintain the pH and Trasylol to inhibit proteolytic activity, then viable islets could be isolated consistently after over 8 hr of storage. These results demonstrate that even short periods of warm ischaemia will render the pancreas unsuitable for islet isolation. Once the pancreas is placed in a suitable cold medium, however, considerable delay may be permissible without adversely affecting the viability of the islets which can be obtained. The same conditions might prove to be applicable when human pancreas is obtained for the purpose of transplantation into diabetic subjects.

Animals

Regulation of insulin and glucagon secretion from a human islet cell adenoma.

The regulation of insulin biosynthesis, and insulin and glucagon secretion have been investigated in a human islet cell adenoma, by incubation of tumour fragments. Both biosynthesis and secretion of insulin were strongly stimulated by incubation of islet tumour cells in the presence of increasing glucose concentrations in the range 2-8 mmol/1. However, 20 mM-glucose or 20 mM-glucose plus isobutyl methylxanthine (IBMX), both of which provide potent secretagogues for normal B cells, failed to stimulate proinsulin biosynthesis and secretion from the tumour cells. Overall rates of secretion, expressed as a proportion of total insulin content, were up to 20-fold higher than those expected for normal pancreatic tissue. Glucagon secretion from the tumour was stimulated by low glucose concentrations; normal A cells also respond in this way under these conditions. However, no stimulation of glucagon secretion occurred in the presence of IBMX. There was therefore a major alteration in the regulation both of insulin and glucagon secretion, in that release of neither hormone was stimulated by cyclic AMP. Ultrastructural examination showed the tumour to be rather heterogeneous. A and B cells with normal storage granule content and structure were seen, as well as a rather larger number of B cells containing some granules of atypical appearance. The insulin content of the tumour (13 i.u./g wet wt) was consistent with 6-8% of the tumour cells being B cells.

Adenoma, Islet Cell

Molar dosage.

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Calcium Chloride