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D B Jones

Publications and source records attributed to D B Jones.

At least 361 records · Page 20Linked to original sources

Effect of omeprazole and polyethylene glycol-400 on antipyrine elimination by the isolated perfused rat liver.

The effect of the substituted benzimidazole, omeprazole, a potent inhibitor of gastric acid secretion, on the hepatic elimination of antipyrine was studied in the rat isolated perfused liver. Bolus dosage (10 mg in 100 ml perfusate) and infusions (1 microgram ml-1 perfusate concentrations) of omeprazole in its solvent, polyethylene glycol-400 (PEG-400), reduced antipyrine clearance by approximately one third (P less than 0.05). PEG-400 alone caused a 15% decrease in antipyrine clearance (P greater than 0.10), indicating that the effect seen with omeprazole was at least partly due to the vehicle of dissolution. A significant but mild choleresis was noted in all preparations (P less than 0.01) exposed to PEG-400. We conclude that the effect of omeprazole on hepatic drug elimination in patients warrants further study.

Animals↗

Use of antibodies to carcinoembryonic antigen and human milk fat globule to distinguish carcinoma, mesothelioma, and reactive mesothelium.

Antibodies raised against human milk fat globule (HMFG 1 and 2) and carcinoembryonic antigen were used in an immunoperoxidase technique to differentiate mesothelioma, carcinoma, and benign, reactive mesothelium. Sixteen mesotheliomas, 27 lung carcinomas, and 13 specimens of reactive mesothelium were examined. Staining for carcinoembryonic antigen was not seen in reactive mesothelium or mesothelioma but was present in 22 of 27 carcinomas. Mesothelioma and carcinoma usually stained with HMFG 1 and 2; reactive mesothelium did not. These three antibodies may help to distinguish carcinoma, mesothelioma, and reactive mesothelium.

Adenocarcinoma↗

A comparison of isocaloric high carbohydrate and high fat test meals in diabetics.

Ten diabetic patients were given test meals at breakfast and lunch on successive days to compare the acute glycaemic responses to meals either high (65%) (HC) or extremely low (12%) in carbohydrate; the latter was very high (71%) in fat (HF). The meals were isocaloric and fibre content, though higher in HC, was within the range of the average British intake for both diets. The mean fasting blood glucose levels were similar on the 2 days (9.8 mmol/l; 9.6 mmol/l) but mean peak post-prandial levels were significantly greater after the HC meals (17.7 mmol/l after breakfast and 14.1 mmol/l after lunch) than after the HF meals (11.7 mmol/litre after breakfast; P less than 0.02; 8.1 mmol/l after lunch; P less than 0.02). Mean blood glucose value for the 6-hr study period was significantly higher after the HC meals (14.0 mmol/l) than after the HF meals (9.2 mmol/l; P less than 0.001). There was no significant difference in mean fasting, peak or total mean triglyceride level. In the short term, therefore, meals very low in carbohydrate and high in fat are followed by a lower glycaemic response than meals high in carbohydrate but with only a usual (22 g/day) fibre content. Delayed gastric emptying after HF meals may well contribute to the results but long-term use of such HF meals is not advised in view of the extremely high fat content.

Blood Glucose↗

Fractionation and further characterization of granulocytic and monocytic alpha-naphthyl acetate (ANAE) esterases.

Following characterization of myeloid nonspecific esterases by isoelectric focusing (IEF), two main groups of alpha-naphthyl acetate (ANAE) esterase isoenzymes were defined and fractionated from cytoplasmic extracts by chromato focusing techniques according to differences in their isoelectric points (pI). The first of these ANAE enzyme groups was common to leukocytes of both granulocytic and monocytic lineage, while the other, which characteristically comprised a group of isoenzymes within the pI range 5.5-6.1, was specifically associated with monocytic differentiation. The properties of the two purified ANAE enzyme fractions were compared by inhibition (heat and sodium fluoride) and further electrophoretic studies, and the results discussed in relation to the cytochemical characterization of these enzymes as markers of specific myeloid cell differentiation.

Carboxylic Ester Hydrolases↗

Suppression of the mixed lymphocyte reaction by alloantigen-primed and -stimulated human spleen lymphocytes.

This communication examines the ability of T cell-enriched preparations from human spleen to suppress lymphocyte proliferation following activation in the mixed lymphocyte reaction (MLR). To enable the generation of a subsequent responding MLR between identical partners to those employed in the initial (stimulating) MLR, spleen T cells were frozen at the time of the first culture. Spleen T cells, stimulated in this way, showed a marked ability to suppress human MLR responses, but HLA-D identity was required for the full expression of suppressor activity. The characteristics of the spleen MLR-induced suppressor T cell resemble closely those described for MLR-generated suppressor T cells in human peripheral blood.

Adult↗

Discrimination between the venous equilibrium and sinusoidal models of hepatic drug elimination in the isolated perfused rat liver by perturbation of propranolol protein binding.

To discriminate between two widely used models of hepatic drug elimination, the venous equilibrium and sinusoidal models, we examined the effect of altering perfusate protein binding on the hepatic elimination of the highly cleared drug, propranolol, by the isolated perfused rat liver. We investigated specifically the relationship between the unbound fraction of drug perfusing the liver and the steady-state unbound drug concentration in hepatic venous effluent (i.e., in the perfusate reservoir) after a constant infusion of drug (1.37 mg/hr) into the portal vein. Each rat liver (n = 21) was perfused over 60 min at one of seven different protein concentrations, such that the unbound fraction of propranolol in the portal venous perfusate was varied from 0.1 to 0.65. The unbound steady-state propranolol concentration in the hepatic venous effluent remained unchanged, despite an almost 7-fold increase in the free fraction of propranolol perfusing the liver. The data conform precisely to the predictions of the venous equilibrium model and are incompatible with the sinusoidal model, which predicts a 100-fold decrease in unbound reservoir concentration. This study therefore establishes that the apparently "unphysiological" venous equilibrium model represents a valid description of the hepatic elimination of this high clearance compound.

Animals↗

Immunological reason for chronic ill health after infectious mononucleosis.

In a group of patients who suffered from chronic ill health after an attack of acute infectious mononucleosis a disorder of T cell regulation was found. By means of cytochemical reactions the staining pattern associated with T suppressor cells was found in a greater percentage and that associated with T helper cells in a smaller percentage than in normal subjects. In a few patients this finding was confirmed in a functional suppressor assay. The patients were unwell for at least a year but most later made a complete recovery, which was associated with return to normal of the lymphocyte subsets.

Adolescent↗

Low phospholipid arachidonic acid values in diabetic platelets.

Platelet aggregation is enhanced in diabetes mellitus, and platelets may be implicated in the pathogenesis of diabetic angiopathy. Increased platelet aggregation is probably mediated by the production of the proaggregatory prostaglandin thromboxane, which is synthesised from arachidonic acid (C20:4) by the action of the platelet enzymes cyclo-oxygenase and thromboxane synthetase. The fatty acid composition of platelet phospholipid was measured in 20 normal controls, 10 insulin-treated diabetics with no or minimal retinopathy, and 10 insulin-treated diabetics with proliferative retinopathy. The percentage of arachidonic acid was significantly higher in controls (mean 22.6%) than in the diabetics with no or minimal retinopathy (mean 18.5%; p less than 0.025) and the diabetics with proliferative retinopathy (mean 14.6%; p less than 0.001). The percentage of linoleic acid was lower in controls (mean 8.9%) than in the diabetics with no or minimal retinopathy (mean 12.6%; p less than 0.01) and diabetics with proliferative retinopathy (mean 13.1%; p less than 0.001). The mean percentage of linolenic acid was significantly lower in the diabetics with proliferative retinopathy (2.7%) than in the normal control group (4.4%; p less than 0.01). A significant negative correlation was found between the percentages of arachidonic acid and glycosylated haemoglobin (Rs = -0.58; p less than 0.001). A significant positive correlation was found between linoleic acid and the percentage of glycosylated haemoglobin (Rs = 0.51; p less than 0.01). The reciprocal correlation between percentages of arachidonic acid and glycosylated haemoglobin suggests that diabetic control may influence thromboxane release and platelet activity directly and that low percentages of arachidonic acid reflect the increased degree of in-vivo activation.

Adult↗

Malignant lymphoma of true histiocytic (monocyte/macrophage) origin.

Since the advent of the newer classifications of non-Hodgkin's lymphoma and the realization that the majority of tumors classified as histiocytic under the Rappaport classification were in fact of lymphocytic origin, there have been remarkably few reports of true histiocytic (monocyte/macrophage) tumors and it has been suggested by some that such tumors should not be considered as a variety of malignant lymphoma. This article describes five patients with malignant lymphoma of neither B- or T-lymphocyte origin in whom the malignant cells could be characterised immunologically, cytochemically, and immunohistochemically as of true histiocytic derivation. The cases showed considerable morphologic diversity but there were shared characteristics at both light microscopic and ultrastructural levels. Positive immunohistochemical staining for alpha 1-antitrypsin was the single most useful criterion in classifying these tumors. Without the use of special techniques there were no clinical or pathologic features that reliably distinguished these cases from non-Hodgkin's lymphomas of lymphocytic derivation. Tumors of histiocytic origin are, therefore, inevitably being included among the non-Hodgkin's lymphomas and are most appropriately classified as such. Identification of histiocytic lymphomas should be encouraged so prognosis and optimum treatment can be established.

Acid Phosphatase↗

Immunohistochemical differentiation between histiocytic and lymphoid neoplasms.

Lysozyme has, until recently, been accepted as the only reliable immunohistochemical marker of benign and malignant histiocytes. Using this marker, very few lymphoreticular neoplasms of histiocytic origin are recognized and more recently alpha-1-anti-trypsin has been shown to be a better marker of malignant histiocytes. By immunizing rabbits with highly purified human blood monocytes we have obtained an antiserum (S22) which stains histiocytes and neutrophils in paraffin sections with a high degree of specificity. Using this antiserum and antisera to lysozyme and alpha-1-anti-trypsin we have stained paraffin sections of tissues containing reactive histiocytes, histiocytic proliferations, leukaemic infiltrates and lymphoreticular tumours of histiocytic and T-cell origin. Our results show that alpha-1-anti-trypsin is the most reliable marker of malignant histiocytes but that the as yet uncharacterized antigen defined by S22 may offer a promising alternative.

Animals↗

Acute and chronic immunological response to dietary antigen.

On separate mornings at 14 day intervals groups of six to eight healthy fasting male volunteers drank a 5.5 MJ test meal containing 20% milk, egg or soya protein, or a control protein free preparation. Using a Clq binding test, marked but transient rises in circulating immune complexes were detected 30-120 minutes after the milk and egg meals but not with soya or the control. No such changes were seen when complexes were measured by Raji cell immunoassay. Food antigen specific antibodies were present in the plasma of all subjects but showed no consistent pattern of variation in the postprandial period. In most volunteers a chronic increase in milk (three weeks) or soya (six weeks) consumption produced no changes in circulating immune complexes or antibodies to dietary protein. Although two of 16 milk and six of 52 soya volunteers had substantial rises of one or more classes of plasma food antigen specific antibodies they were matched by a similar number in which a decrease was recorded. These results indicate that the formation of circulating immune complexes may be a physiological response to a large load of dietary antigen but that in most adults a chronic increase of milk or soya consumption does not affect food antibody or immune complex concentrations.

Adult↗

Preliminary report of an association between measles virus and achalasia.

Complement fixation tests were performed on sera from 18 patients with achalasia and 12 age- and sex-matched controls against a number of bacterial and viral agents in an attempt to ascertain any association with previous infection or any evidence of an altered immune response. There was a statistically significant increase of antibody titre against measles virus in the sera of 21 patients with achalasia compared with age- and sex-matched controls and this was confirmed by haemagglutination inhibition.

Adult↗

Changes in blood pressure and renal function after parathyroidectomy in primary hyperparathyroidism.

Changes in blood pressure and renal function were investigated in 62 patients with primary hyperparathyroidism treated surgically, in an attempt to assess whether or not hypertension and renal impairment should be regarded as important indications for parathyroidectomy. 29% were hypertensive pre-operatively and the blood pressure remained elevated after parathyroidectomy in all of these patients. Hypertension developed for the first time after parathyroidectomy in 45% of those patients who were normotensive before surgery. Renal function was normal initially in 73% and mild renal impairment developed after surgery in 9% of these patients. At the end of the follow-up period, the prevalence of hypertension was higher in patients with renal impairment pre-operatively (88%) than in those with normal renal function (51%). We conclude that hypertension alone should not be regarded as an indication for parathyroidectomy in asymptomatic hyperparathyroidism. No firm conclusions can be reached about the importance of mild renal failure as an indication for surgery and the question is unlikely to be resolved without conducting a prospective controlled trial.

Blood Pressure↗

Communicating hydrocephalus in the intellectual deterioration of diabetes mellitus.

Atherosclerosis of cerebral vessels (Grunnet 1963) and hypoglycaemia (Bale 1973) are thought to be involved in the premature intellectual deterioration which occurs in some diabetics. Two diabetics are now reported who, in the course of their investigation for intellectual deterioration, were found to have communicating hydrocephalus.

Diabetes Complications↗

Hepatotoxicity of sodium valproate.

Repeated clinical and biochemical evaluations of liver function were performed on 60 patients taking sodium valproate. No clinical evidence of liver disease was found. Biochemical abnormalities were frequently found, but they were far more common in patients treated with multiple anticonvulsants than in patients on valproate alone. A control group of patients taking phenytoin or carbamazepine monotherapy also had a high incidence of biochemical abnormalities. A group of patients started on valproate therapy 6 years previously was followed up. No evidence of liver disease was found in this group. It was concluded that biochemical abnormalities of liver function in patients receiving valproate are not progressive, and in many cases relate to the intake of other drugs. The finding of abnormal liver function tests is not necessarily an indication for ceasing valproate.

Adolescent↗