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Biomedical subjects

T Jones

Publications and source records attributed to T Jones.

At least 415 records · Page 23Linked to original sources

Measurement of blood flow, oxygen utilisation, oxygen extraction ratio, and fractional blood volume in human brain tumours and surrounding oedematous tissue.

The blood flow, oxygen utilisation, oxygen extraction ratio, and fractional blood volume were measured in brain tumours and the surrounding cerebral tissues. A total of 21 patients were studied. These included 10 primary tumours, eight secondary and three with unknown histology. Measurements were performed using the oxygen-15 steady state inhalation technique and positron emission tomography. Within the tumours no relation between blood flow, oxygen utilisation and blood volume was found. In all tumours oxygen supply was in excess of the oxygen demand of the tissues as reflected in oxygen extraction ratios that were lower than those of normal brain tissue. No indication of local ischaemia in peritumour oedema was found.

Blood Volume↗

Rate of clearance of interleukin-1 from the blood of normal and nephrectomized rats.

Interleukin-1 (IL-1), a macrophage product, appears to be responsible for a wide variety of changes in animals during the early stages of infection and inflammation. However, the fate of injected IL-1 has not been established. The major pathway of removal from the circulation may be through the kidney, since IL-1 can be found in urine. The IL-1 for these studies was prepared from peritoneal macrophages of rats and rabbits. The clearance rate of IL-1 was determined by measuring the activity, for increasing plasma fibrinogen or releasing bone marrow neutrophils, which remained in the blood at various times after an iv injection. Both rat and rabbit IL-1 were removed rapidly from the blood of rats. The results indicate that less than 10% of the IL-1 was cleared by the kidney. So that rats with their kidneys removed showed only a slight decrease in the clearance rate of IL-1. This suggests that excretion through the kidney does not represent the major mechanism of IL-1 disposal.

Animals↗

The role of a human antigen specific T8+ cell subset in antigen presentation, helper function and contrasuppression.

Regulation of the human immune response was studied by sequential separation of subsets of T cells, followed by assessment of their helper and suppressor functions in a series of reconstitution experiments. T8+ lymphocytes were separated by panning on streptococcal antigen (SA) coated plates into T8+ SA-adherent cells (T8+SA+) and T8+ SA-non-adherent cells (T8+SA-). The helper and suppressor functions of the T8+SA+ and T8+SA- cells, reconstituted with T4+ helper cells were then studied by a direct antibody forming cell assay. T4+ cells will not induce helper activity by 1000 ng SA alone but require the accessory function of monocytes (Mo). However, replacing Mo by T8+SA+ cells will elicit a similar helper activity by T4+ cells and SA as that induced by Mo. In addition to the antigen-specific presentation and induction of helper activity, the T8+SA+ subset displays the properties of antigen-specific contrasuppressor cells. Thus, reconstitution of T4+ cells and T8+SA- (suppressor cells) with T8+SA+ and 1000 ng SA induces helper and no suppressor activity. Substitution of Mo for the T8+SA+ cells converts the helper to a predominantly suppressor-cell function. T8+SA- cells elicit suppression with 1 ng SA in the absence of accessory cells and reconstitution with Mo, T8+SA+ or T4+ cells failed to affect the suppressor activity. Total reconstitution of the four principle subsets of T4+, T8+SA+, T8+SA- cells and Mo elicited similar antigen dose-dependent responses as those of the unseparated mononuclear cells. It seems that all four cell subsets are required for optimal immunoregulation. We suggest that the T8+SA+ can present antigen to T4+ helper cells and induce helper activity, but in addition these cells can prevent the suppressor subset of T8+ cells from inhibiting T4+ helper cells and function as contrasuppressor cells. The mechanism of these functions is not known but HLA class II antigens might play an essential role in antigen binding, presentation and contrasuppression of the T8+SA+ cells, as the latter are significantly enriched in Ia+ cells.

Antibody Formation↗

Separation and characterization of a subset of human T8+ cells which function as antigen-presenting and contrasuppressor cells.

The lectin Vicia villosa (VV) binds preferentially a subset of T cells. Separated VV-adherent cells (AC) do not generate helper function alone, but when added to VV-non-adherent cells (NAC), they can present streptococcal antigen (SA) and induce helper function as effectively as monocytes, at a ratio of 1 VV-AC to 4 VV-NAC. Further separation into a T8+ subset of VV-AC and reconstitution with T4+ helper cells (HC) has established that the T8+ VV-AC induces T4+ cells to helper activity. However, in addition to antigen presentation, the T8+ subset of VV-AC has a contrasuppressor function, for it can prevent T8+ suppressor cells from inhibiting T4+ HC function. The results suggest that a T8+ subset can present antigen to T4+ HC, activate helper function and prevent suppression. The T8+ VV-AC may have considerable biological significance in its dual function of countering the dominant suppressor activity and presenting antigen to induce helper activity.

Antibodies, Monoclonal↗

The helper and suppressor functions of primate T cells elicited by a 185K streptococcal antigen, as compared with the helper function elicited by a 4K streptococcal antigen.

Helper and suppressor functions of human T lymphocytes that act on antibody-forming B cells were elicited by a large 185K streptococcal cell wall antigen. However, a small 4K streptococcal peptide elicited helper but no suppressor function. These differences in the functional activities of the large and small m.w. streptococcal antigens (SA) were confirmed by direct immunisation of rhesus monkeys with the 185K-SA and 4K-SA. Sequential studies have shown that whereas the 185K-SA elicits dose-dependent helper and suppressor activities, the 4K-SA elicits only helper function. Cell-depletion studies with human cells suggest that removal of T8+ cells by killing with OK.T8 and complement leads to a loss of suppressor and a broadening in the concentration of 185K-SA, which elicits helper activity. Because the 4K-SA does not elicit suppression, removal of T8+ cells does not affect this function. However, similar depletion of T4+ cells results in loss of the helper activities, both with the 185K-SA and 4K-SA, and again a broadening in the concentration of the 185K-SA, which elicits suppression. Direct comparison by autoradiography between 125I-labeled 185K-SA and 4K-SA suggests that both antigens can bind directly to monocytes or T8+ VV+ cells. Furthermore, both antigens can induce helper function if T4+ cells are reconstituted with either monocytes or T8+ VV+ cells. Attempts will now be made to sequence the amino acid determinants of the 185K-SA, so as to define the epitopes responsible for the two major regulating functions elicited by this antigen.

Animals↗

Comparison of total parenteral nutrition with 25 per cent and 45 per cent branched chain amino acids in stressed patients.

Administration of total parenteral nutrition (TPN) solutions high in branched chain amino acids (BCAA) is thought to improve metabolic support during stress. This prospective, randomized, double blind study compared 45 per cent BCAA with 25 per cent BCAA in 12 patients. Seven patients had multiple trauma; two, gastrointestinal surgery; one, pancreatitis; and two, cirrhosis. The TPN regimen was 1.0-1.5 gm/kg/day amino acids and 30-45 glucose kcal/kg/day. The BCAA formula used was high in isoleucine and valine, but not leucine. Amino acid plasma levels, blood chemistries, 3-methylhistidine excretion, and nitrogen balance were studied. Control studies showed negative nitrogen balance (-7.1 +/- 2.9 gm) (mean +/- SEM), elevated insulin (61 +/- 21 microunit/ml), and elevated 3-methylhistidine (3MH) excretion (688 +/- 309 micromol); plasma leucine (93 +/- 11 nmol/ml) and isoleucine (37 +/- 23) were low, and valine (155 +/- 20) was elevated. Plasma methionine (40 +/- 9) and tyrosine (70 +/- 12) were high normal. Phenylalanine (85 +/- 5) was elevated. Both groups showed increased nitrogen excretion and positive nitrogen balance during the study (25 per cent, 2.0 +/- 1.4 gm/day; 45 per cent, 1.2 +/- 2.6 gm/day). Three-methylhistidine excretion changed little in either group (557 +/- 149, 414 +/- 91), insulin rose (135 +/- 27, 65 +/- 19), and plasma leucine (82 +/- 4, 71 +/- 9) changed little. Plasma isoleucine (51 +/- 3, 155 +/- 16) and valine (173 +/- 11, 691 +/- 23) both rose, more in the 45 per cent group. Methionine (67 +/- 12, 37 +/- 4) and tyrosine (51 +/- 6, 50 +/- 10) changed little.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Recording the consultation: model for assessment.

A model has been devised that provides at a glance, a summary of the relative importance of the physical, psychological, and social aspects of a patient's problem as assessed at the consultation. Its presence in the notes, alongside a medical diagnosis, allows treatment to be planned along recognised lines, while still keeping other aspects of the problem in perspective. It is suggested that this may lead to more appropriate management.

Family Practice↗

Evaluation of cerebral perfusion reserve in patients with carotid-artery occlusion.

Regional cerebral blood flow, oxygen utilisation, fractional oxygen extraction, and cerebral blood volume were measured by positron emission tomography in thirty-two patients with internal-carotid-artery occlusion. In most cases, and reduction in cerebral blood flow in the territory distal to an occluded carotid artery was matched to diminished cerebral metabolic demands. Cerebral blood flow was inappropriately low in only six patients, in whom regional oxygen utilisation was maintained by a compensatory rise in oxygen extraction ratio. The frequent finding of high cerebral blood volume distal to occluded vessels was consistent with a state of focal vasodilatation in response to diminished cerebral perfusion pressure. Analysis of the relation between cerebral blood flow, blood volume, and oxygen extraction ratio suggested that the reduction in cerebral perfusion pressure, and hence circulatory reserve, could be most reliably predicted by the ratio of cerebral blood flow to blood volume. By identifying those patients with carotid occlusion who are most compromised on haemodynamic grounds, combined measurement of cerebral blood flow and blood volume should be valuable in selection of candidates for extracranial-intracranial bypass surgery.

Arterial Occlusive Diseases↗

Evaluation of cerebral perfusion reserve in patients with carotid-artery occlusion.

Regional cerebral blood flow, oxygen utilisation, fractional oxygen extraction, and cerebral blood volume were measured by positron emission tomography in thirty-two patients with internal-carotid-artery occlusion. In most cases, any reduction in cerebral blood flow in the territory distal to an occluded carotid artery was matched to diminished cerebral metabolic demands. Cerebral blood flow was inappropriately low in only six patients, in whom regional oxygen utilisation was maintained by a compensatory rise in oxygen extraction ratio. The frequent finding of high cerebral blood volume distal to occluded vessels was consistent with a state of focal vasodilatation in response to diminished cerebral perfusion pressure. Analysis of the relation between cerebral blood flow, blood volume, and oxygen extraction ratio suggested that the reduction in cerebral perfusion pressure, and hence circulatory reserve, could be most reliably predicted by the ratio of cerebral blood flow to blood volume. By identifying those patients with carotid occlusion who are most compromised on haemodynamic grounds, combined measurement of cerebral blood flow and blood volume should be valuable in selection of candidates for extracranial-intracranial bypass surgery.

Adult↗

Positron emission tomography for in-vivo measurement of regional blood flow, oxygen utilisation, and blood volume in patients with breast carcinoma.

Regional blood flow, oxygen extraction ratio, and oxygen utilisation were measured in nine patients with breast carcinoma by means of the oxygen-15 steady-state inhalation technique and positron emission tomography. Regional blood volume was measured by means of tracer amounts of carbon-11-labelled carbon monoxide. The regional blood flow was consistently higher in non-necrotic tumour tissue than in surrounding normal breast tissue or contralateral normal breast. Oxygen utilisation was slightly higher in the tumour. The regional oxygen extraction ratio (ie, the fraction of oxygen extracted from the nutritional blood supply) was appreciably lower in the tumour than in normal breast tissue. These findings suggest that there is, at least on a macroscopic level, no supply-limited impairment of respiration in human breast cancer.

Aged↗

Positron emission tomographic studies in aging and cerebrovascular disease at Hammersmith hospital.

This paper attempts to place into perspective the present state of clinical investigation with PET in neurology. To this end we briefly review the work of the neurology group of the MRC Cyclotron Unit at Hammersmith Hospital, by reference to studies performed in normal subjects and in patients with cerebrovascular disease. Based on the current understanding of human physiology in health and disease as a result of this new method of clinical measurement in humans, we speculate on some possible future developments and present constraints in the application of PET to clinical research.

Acute Disease↗

Positron emission tomography of the brain: new possibilities for the investigation of human cerebral pathophysiology.

In the foregoing an overview of positron emission tomography has been presented. Its theoretical, technical, and methodological implications, as well as its clinical applications have been outlined. The emphasis has been on the quantitative aspects of the method and its usefulness is investigating normal and pathological functions of brain tissue. Although the potential of this new research technique is obvious, many theoretical and practical difficulties still need to be solved. Nevertheless it provides an opportunity to bridge the gap between basic experimental research and clinical medicine.

Aging↗

Measurement of cerebral blood flow using bolus inhalation of C15O2 and positron emission tomography: description of the method and its comparison with the C15O2 continuous inhalation method.

This article describes a rapid method for the regional measurement of cerebral blood flow using a single breath of C15O2 and positron emission tomography. The technique is based on the bolus distribution principle and utilises a reference table for the calculation of flow. Seven subjects were studied using both this method and the C15O2 continuous inhalation steady-state technique. The single-breath method gave flow values 20% higher than those obtained using the steady-state method. A simulation study was performed in an attempt to define the reasons for the difference between the two techniques. Estimations were made of identified sources of error in the measurement of regional cerebral blood flow using the single-breath technique and compared with results from a similar study previously described for the steady-state technique. However, further comparative studies will be necessary to satisfactorily explain the difference between both techniques.

Adult↗

In vivo measurement of regional cerebral haematocrit using positron emission tomography.

A method is described for measuring the regional cerebral-to-large vessel haematocrit ratio using inhalation of carbon-11-labelled carbon monoxide and the intravenous injection of carbon-11-labelled methyl-albumin in combination with positron emission tomography. The mean value in a series of nine subjects was 0.69. This is approximately 20% lower than the value of 0.85 previously reported. It is concluded that previous measurements of regional cerebral blood volume using a haematocrit ratio of 0.85 will have underestimated the value of regional cerebral blood volume by 20%.

Albumins↗

Measurement of regional cerebral pH in human subjects using continuous inhalation of 11CO2 and positron emission tomography.

The cerebral pH of four normal human subjects has been measured using continuous inhalation of 11CO2 and positron emission tomography (PET). 11CO2 was administered to each subject at a constant rate for 15 min, during which time serial arterial plasma 11C levels were determined and serial 11C cerebral uptake PET scans were performed at a fixed axial tomographic level. 11C uptake kinetics were analysed using a three-compartment model. Rate constants have been estimated for the free exchange of 11CO2 between plasma and cerebral compartments for each subject, and their cerebral pH calculated. Whole brain pH values ranged from 6.96 to 7.05, and no significant pH difference between regions containing predominantly grey or white matter was noted. Best fits to 11C uptake data were achieved by effectively neglecting the metabolic fixation of 11C by cerebral tissue. The purpose of this study was to test the feasibility of pH measurement using the 11CO2 continuous inhalation technique. It is concluded from the results and the error analysis that continuous 11CO2 inhalation combined with PET is potentially a simple and useful method for determining regional cerebral pH.

Brain↗