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Biomedical subjects

T Jones

Publications and source records attributed to T Jones.

At least 433 records · Page 24Linked to original sources
PubMed1984

A method to quantitate the fractional extraction of rubidium-82 across the blood-brain barrier using positron emission tomography.

Previously, rubidium-82 and positron emission tomography (PET) have been used to assess qualitatively the integrity of the blood-brain barrier (BBB). In this report, a method is described to measure the fractional extraction of rubidium across the BBB using the constant intravenous infusion of rubidium-82. In addition, the continuous inhalation of oxygen-15-labelled carbon dioxide is needed to measure regional CBF, and it is also necessary to measure regional cerebral blood volume. The assumptions underlying the model are identified, and the impact of deviations from these assumptions is described. From radiation dose and statistical considerations, it is shown that for normal cerebral tissue and the PET scanner used in this study, the rubidium extraction fraction can be quantitated only for regions as large as a cerebral hemisphere. However, quantitation is also possible for smaller regions where the focal extraction of rubidium is increased.

Blood-Brain Barrier↗
PubMed1984

Quantitative measurement of blood-brain barrier permeability using rubidium-82 and positron emission tomography.

In normal brain, the blood-brain barrier (BBB) is highly impermeable to K+ cations, their transport being controlled by ATPases situated in the endothelial cell membranes. 82Rb+ is a positron-emitting analogue of K+ with a half-life of 75 s. Using a steady-state model and positron emission tomography, quantitative extraction data for 82Rb+ transport across the BBB have been obtained both in normal human subjects and in a variety of conditions of cerebral pathology. A mean cerebral Rb extraction of 2.1% was found for normal subjects, corresponding to a mean value of 1.1 x 10(-6) cm s-1 for 82Rb+ cation permeability across the BBB. No increase in cerebral Rb extraction was observed for patients with diffusely raised intracranial pressure secondary to obstructive hydrocephalus and benign intracranial hypertension, or for patients with multiple sclerosis or cerebral systemic lupus erythematosus. Cerebral tumours that were enhanced on computed tomography scanning showed a significant increase in local Rb uptake. No correlation between tumour size, or grade of glioma, and tumour Rb extraction was found. Nonenhancing tumours showed no increase in local Rb extraction, and regions of perifocal tumour oedema also had Rb extraction values in the normal range. It is concluded that increased Rb extraction occurs only where tight junction integrity in the BBB breaks down locally, that is, in the microcirculation of enhancing tumours but not in that of perifocal regions of tumour oedema or nonenhancing tumours.

Adult↗
PubMed1984

Different mechanisms for the relief of angina after coronary bypass surgery. Physiological versus anatomical assessment.

To determine the physiological effect of coronary artery bypass surgery and the mechanisms for pain relief, 15 patients with exertional angina were studied before and after operation. Before the operation conventional tests included exercise tests (all positive) and coronary angiography (all patients had greater than or equal to 70% stenosis of major vessels). In addition, ambulatory electrocardiographic monitoring during 48 hours detected 92 episodes (greater than or equal to 1 mm) of ST depression. Regional myocardial perfusion was assessed with positron tomography using rubidium-82 (t1/2 78 s) and this showed reversible inhomogeneity with absolute regional reduction of cation uptake after exercise in all 15 patients. After coronary surgery 10 of the 15 patients had (a) no angina, (b) patent grafts (three or more), (c) no evidence of ischaemia during ambulatory monitoring out of hospital, and (d) homogeneous perfusion with reversal of the disturbances in regional myocardial perfusion after exercise. After operation one of the 15 patients had no angina and showed silent infarction in the segment that was previously ischaemic but supplied by a patent graft. All but one of the remaining patients had no angina, patent grafts, but disturbances of regional myocardial perfusion with silent ischaemia on exercise. Two of these patients continued to have asymptomatic and ischaemic episodes of ST depression during ambulatory monitoring out of hospital. This physiological study of regional myocardial perfusion in patients in hospital and in those with ischaemia out of hospital showed that three different mechanisms may account for the relief of pain--improved perfusion, infarction, and silent ischaemia. Silent ischaemia in particular raises puzzling pathophysiological and therapeutic questions that may affect prognosis and the interpretation of clinical trials.

Adult↗
PubMed1984

Studies on regional cerebral oxygen utilisation and cognitive function in multiple sclerosis.

Regional cerebral oxygen utilisation (rCMRO2), oxygen extraction (rOER), blood flow (rCBF), and blood volume (rCBV) have been determined for fifteen patients with multiple sclerosis in remission using positron emission tomography (PET). Cerebral oxygen utilisation and blood flow were significantly reduced in both white matter and peripheral cortical grey matter in the multiple sclerosis patients compared to a group of normal controls. No evidence of regional cerebral ischaemia in the multiple sclerosis group was found. Lowest levels of cerebral oxygen utilisation were found in patients with cerebral atrophy, and in patients in whom a significant fall in present full-scale IQ from estimated pre-morbid levels had occurred. No correlation was found between rCMRO2 values and severity of locomotor dysfunction or clinical disease duration.

Adult↗
PubMed1984

Every bunny benefits.

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Anniversaries and Special Events↗
PubMed1984

The role of MHC class II antigenic determinants in the function of human antigen binding T8+ cells, monocytes and helper and suppressor factors.

The role of MHC class II antigens was investigated in the process of antigen binding by T8+ cells and monocytes (Mo) and in the functions of helper factor (HF) and suppressor factor (SF). Monoclonal antibodies (MoAbs) to HLA-DR, DC and SB determinants were used in immunofluorescence, inhibition of antigen binding and affinity chromatography of HF and SF. Indirect immunofluorescence studies suggest that T lymphocytes from peripheral blood of healthy subjects have a small proportion of cells expressing HLA-DR, beta chain determinants (1.4-3.8%). These belong predominantly to the T8+ subset of cells (4.6-8.8%), with only a very small proportion in the T4+ cells (0.1-1.8%). However, DC1 on DRw6+ T cells and SB2,3 on any HLA typed cells were found in significantly greater proportion than the DR antigens in both T8+ and T4+ cells, though this was again greater on T8+ (30 and 25%) than T4+ (8.3 and 14.4%) cells. Although Mo had a greatly increased proportion of cells with DR-beta chain determinants (27-45%) than the T8+ cells, the converse was found with DC1 and SB2,3 determinants (13.9 and 11.4%). Inhibition of 125I-streptococcal antigen (SA) binding to T8+ cells and to Mo by MoAbs to the class II antigens showed that DR-beta chain monomorphic or polymorphic antibodies and DC1 antibodies inhibited binding to both cell types by 66-94%. However, MoAbs to DR-alpha chains or to the SB2,3 determinant failed to yield significant inhibition. Affinity chromatography studies of HF and SF revealed that the DR-beta chain monomorphic and DC1 antibodies bound HF and SF activities and that this was not found with the DR-beta chain polymorphic or SB2,3 antibodies. The results of inhibition of 125I-SA binding to T8+ cells and Mo, and absorption of HF and SF by affinity chromatography with MoAbs suggest four categories of recognition of human MHC class II antigenic determinants. (1) Class II determinants shared by the T8+ cells, Mo, HF and SF and recognized by MoAbs to monomorphic beta chains (DA6.231) and to DC1. (2) Class II determinants shared only by the SA binding T8+ cells and Mo and recognized by the MoAbs to a polymorphic beta chain (DA6.164) and to a monomorphic DR determinant (OK.Ial). (3) Class II determinants shared only by the HF and SF and recognized by the MoAbs to one of the alpha chains (TAL.1B5). (4) Class II determinants not detected on the two cells or the two T cell factors.

Antibodies, Monoclonal↗
PubMed1984

Detection of cross-reacting murine I-J like determinants on a human subset of T8+ antigen binding, presenting and contrasuppressor cells.

Murine I-J gene products have been found in T suppressor cells (SC) and factors, macrophages and contrasuppressor cells (CSC). However, a human counterpart of the murine I-J has not been reported. As there is strong evidence that some murine anti-Ia antisera cross-react with human Ia antigens, the possibility was tested that mouse anti-I-J antibodies might cross-react with corresponding human class II determinants. Indeed, this revealed that three anti-I-J monoclonal antibodies (MoAb) and two antisera tested react with human mononuclear cells and that a significantly greater proportion of T8+ than T4+ cells or monocytes (Mo) react with the I-J antibodies. This was corroborated by autoradiography with significant inhibition of 125I-SA (streptococcal antigen) binding to T8+ cells but not to Mo by the MoAb or antisera to murine I-J. Functional reconstitution experiments of T4+ helper cells with the SA binding and presenting T8+ Vicia villosa adherent cells (VV-AC) and assessment of specific antibody forming cells to SA suggest that the antigen presenting function of this T8+ subset can be significantly inhibited by killing with the MoAb to I-J and complement. Furthermore, the subset of T8+ VV-AC also functions as CSC, for killing with MoAb to I-J and complement significantly inhibited the contrasuppressor function. This is consistent with the presence of I-J gene products in murine CSC. However, similar treatment of T8+ VV-NAC (non-adherent cells) or monocytes (Mo) failed to affect the suppressor or accessory helper function of these cells, respectively. Phenotypic characterization, inhibition of 125I-SA binding and reconstitution experiments for helper and suppressor functions, suggest that a subset of T8+ antigen binding, presenting and CSC may express determinants cross-reacting with murine I-J molecules.

Animals↗
PubMed1984

A comparative study of streptococcal antigen-binding human T8+ cells and monocytes, in relation to the HLA-DRw6 locus and the helper, suppressor and contrasuppressor functions.

Binding of streptococcal antigen was compared between T8+ cells and monocytes (Mo) from DRw6+ and DRw6- subjects. Both T8+ cells and Mo from DRw6- subjects bind streptococcal antigen (SA) specifically and almost entirely at a concentration of 1000 ng per 0.1 ml. However, the DRw6+, T8+ cells bind SA at a concentration of 1 ng but the DRw6+ Mo bind SA at both 1 and 1000 ng of SA per 0.1 ml. The HLA-DR-dependent shift in the binding concentration of SA applied to Mo as well as T8+ cells, except that the DRw6+ Mo showed a biphasic response (1 and 1000 ng) of SA binding. Comparative inhibition studies revealed that the antigen binding T8+ cells, unlike Mo, are inhibited with monoclonal anti-T8 and -T5 antibodies and anti-suppressor factor antiserum. Neither cell was inhibited by anti- T4, M1, F(ab), IgG, IgM, VH null cell or helper factor antibodies, and anti-T3 antibodies showed variable inhibition of SA binding to T8+ cells but no inhibition to Mo. A functional comparison was carried out between the antigen binding cells and helper and suppressor activities in unseparated mononuclear cells. T4-depleted and T8-depleted populations of cells. The concentration of SA binding to the T8+ cells was the same as that required to elicit helper activity but reciprocal to the broad range of SA concentrations necessary to induce suppressor cell activity. The results are interpreted on the basis of the hypothesis that the antigen binding T8+ cell functions as a contrasuppressor cell which prevents the major subset of the T8+ cells inhibiting the T4+ cells.

Antigens, Bacterial↗
PubMed1983

Direct photoaffinity labeling of the catalytic site of mouse ribonucleotide reductase by CDP.

Ribonucleotide reductase reduces all four ribonucleoside diphosphates to the deoxyribonucleotides required for DNA synthesis. The enzyme is composed of two nonidentical subunits, M1 and M2. The 89-kilodalton M1 subunit contains at least two allosteric sites which, by binding nucleotide effectors, regulate the catalytic activity and substrate specificity of the enzyme. We now show that in addition, protein M1 contains a substrate-binding (catalytic) site which is specifically photolabeled after UV irradiation in the presence of the natural substrate, [32P]CDP. The photolabeling of protein M1 by [32P]CDP required the presence of the second subunit, protein M2, and ATP, the positive allosteric effector for CDP reduction. The negative effectors, dATP, dGTP, and dTTP, inhibited the photolabeling of wild type protein M1. Deoxy-ATP did not inhibit the labeling of a mutant protein M1 that is resistant to feedback inhibition by dATP. In addition, hydroxyurea and 4-methyl-5-aminoisoquinoline thiosemicarbazone, two inhibitors of ribonucleotide reductase which affect protein M2, also inhibited the [32P]CDP labeling of protein M1. These data provide new insights into the role and interaction of the two ribonucleotide reductase subunits, proteins M1 and M2, and the mechanism of action of the allosteric effectors.

Affinity Labels↗
PubMed1983

In vivo disturbance of the oxidative metabolism of glucose in human cerebral gliomas.

Abnormalities in the oxidative metabolism of glucose in human cerebral gliomas have been studied in seven patients using positron emission tomography. Measurements of regional cerebral blood flow and oxygen consumption were obtained using the oxygen-15 steady-state inhalation technique. Values of regional cerebral glucose consumption were obtained using fluorine 18-labeled 2-fluoro-2-deoxy-D-glucose and a simplification of the method of Sokoloff. Functional values were obtained for regions of tumor and brain tissue in the middle cerebral artery territory of the contralateral cortex. Values of regional glucose consumption were calculated for both regions using a value of the lumped constant quoted for normal brain tissue (0.42). Tumor regional cerebral blood flow was comparable to that in the contralateral cortex, whereas regional cerebral oxygen consumption was depressed. This depression resulted in low tumor values of the fractional oxygen extraction ratio (0.21 +/- 0.07), indicating that oxygen supply exceeded the metabolic demand. In contrast, tumor regional cerebral glucose consumption was not depressed and regional glucose extraction ratios were similar for tumor and brain tissue. The metabolic uncoupling between regional oxygen consumption and regional glucose consumption (CMRO2/CMRGlu = 0.24 +/- 0.07 ml of oxygen per milligram of glucose) is indicative of increased aerobic glycolysis.

Adult↗
PubMed1983

Disturbance of oxidative metabolism of glucose in recent human cerebral infarcts.

Eight patients with recent cerebral hemispheric infarction were studied with positron emission tomography and the oxygen-15 steady-state inhalation and [18F]deoxyglucose techniques to obtain values of regional cerebral blood flow, oxygen consumption, and glucose metabolism. The Sokoloff equation, used to calculate glucose metabolism, was simplified to exclude the exponential terms containing the rate constants. A value of the lumped constant quoted for normal brain (0.42) was used for infarcted regions and contralateral hemisphere. Mean regional cerebral blood flow, oxygen consumption, and glucose metabolism were all significantly depressed within the infarcts compared with the mirror regions in the contralateral cerebral hemisphere. The mean fractional extraction of oxygen was low, indicating an adequate supply of oxygen for residual oxidative metabolism. Regional oxygen consumption and glucose metabolism were significantly correlated within the infarcts, but with a relationship of 2 moles of oxygen per mole of glucose--one-third that in the contralateral hemisphere and in normal brain. Although these results suggest that the metabolizing tissue of a recent cerebral infarct utilizes aerobic glycolysis, caution about the validity of this pathophysiological observation is dictated by limitations in current positron emission tomographic tracer methodology.

Adult↗
PubMed1983

Prevention of adriamycin toxicity.

Mice treated with lethal doses of adriamycin (A1) (IP) are rescued with a single IP dose of 3,5,5-trimethyl-2-morpholinon-3-yl radical dimer (TM3). The in vivo rescue is assumed to be analogous to the in vitro reaction of TM3 with A1 that produces the non-toxic 7-deoxy-adriamycinone (7dAone). TM3 prevents death if given within 60 min following A1 administration. Control A1-treated mice died by 8 days (median survival time) whereas TM3 rescued A1-treated mice had a median survival time of greater than 60 days.

Animals↗