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Biomedical subjects

D B Jones

Publications and source records attributed to D B Jones.

At least 307 records · Page 17Linked to original sources

Leiomyosarcoma of the uterus with giant cells resembling osteoclasts.

A case of leiomyosarcoma of the uterus with osteoclast-like giant cells was examined by light and electron microscopy, histochemistry, and immunoperoxidase techniques. A panel of antibodies was used, including monoclonal antibodies raised against various macrophage determinants and PD 7/26, which detects a leucocyte-common antigen. The giant cells contained nonspecific esterase, stained with PD 7/26 and with two antimacrophage antibodies. These findings strongly suggest that these giant cells are derived from macrophages.

Antibodies, Monoclonal↗

The disposition of intravenous L-tryptophan in healthy subjects and in patients with liver disease.

The disposition of free and of total tryptophan following an intravenous load of 1.5 g of L-tryptophan was evaluated in eight patients with non-cirrhotic liver disease, 40 patients with cirrhosis of the liver (21 Child's A, 15 Child's B, 4 Child's C) and in 14 healthy subjects. Cirrhosis affected disposition of tryptophan by (a) decreasing the clearance of both free and total tryptophan by 64% (P less than 0.001) and 34% (P less than 0.01), respectively, (b) by increasing the apparent volume of distribution of total tryptophan by 42% (P less than 0.01) by expansion of the peripheral compartment, resulting in (c) a threefold increase in the half-life of tryptophan. Apart from a reduction in free tryptophan clearance, these changes in tryptophan disposition were not apparent in patients with non-cirrhotic liver disease. Elevated fasting free tryptophan plasma concentrations are an indicator of impaired tryptophan metabolism in cirrhosis. They result from a decreased hepatic clearance of tryptophan rather than from a reduction in tryptophan protein binding. This study emphasises the markedly differing pharmacokinetic behaviour of tryptophan in cirrhotic patients compared with normal subjects and with patients with non-cirrhotic liver disease.

Adult↗

The effectiveness of ranitidine in reducing gastric acid-secretion decreases with continued therapy.

To examine whether changes in inhibition of gastric acid secretion occur during chronic ranitidine therapy, duodenal ulcer patients in remission were studied before and after 9 months of maintenance ranitidine therapy (150 mg nocte). At each time, the effect of a bolus i.v. dose of ranitidine (50 mg) on pentagastrin-stimulated maximal acid output was measured. Oral and intravenous pharmacokinetic studies were also performed to examine whether changes in absorption or disposition occur during long-term dosage. After 9 months' therapy, ranitidine inhibited pentagastrin-stimulated secretion by a median of 62%, substantially less than the median inhibition of 95% pre-treatment. Median acid output in the period 60-120 min post-ranitidine was six times the pretreatment value. Since pharmacokinetic parameters were unaltered, this reduced ability to inhibit acid output appears to indicate reduced sensitivity of acid secreting mechanisms to ranitidine after prolonged dosage.

Administration, Oral↗

Spinal cord compression as the first presentation of lymphoma--a review of 15 cases.

Fifteen cases are described in which the first presentation of lymphoma was acute spinal cord compression. Lymphoma was diagnosed in laminectomy biopsy specimens using a combination of conventional histological techniques and immunohistochemistry. The patients were predominantly middle-aged or elderly men, some of whom were subsequently shown to have disseminated lymphoma. In other cases, however, the disease was apparently localized to the spine. The tumours consisted of 11 B-cell diffuse follicle centre cell lymphomas, three T-cell lymphomas and one lymphoblastic lymphoma. Following treatment, generally by laminectomy and radiotherapy, some patients have made good recoveries, especially where the disease was localized in the spine.

Adult↗

Platelet aggregation in non-insulin-dependent diabetes is associated with platelet fatty acids.

Platelet aggregation was measured in 15 patients having non-insulin-dependent diabetes mellitus (NIDDM) at the time of diagnosis and after three months of dietary treatment. Mean fasting plasma glucose fell from 13.0 to 8.8 mmol/l (p less than 0.0002), glycosylated haemoglobin fell from a mean of 11.3% to 9.0% (p less than 0.005) and insulin levels fell from a mean of 17.5 to 13.8 mU/l (p less than 0.005). Platelet aggregation showed a variable response and did not correlate with plasma glucose, glycosylated haemoglobin or plasma insulin. Multiple linear regression analysis was carried out on the aggregation values against the biochemical variables and platelet phospholipid fatty acid levels following logarithm transformation. Platelet linolenic acid and eicosapentaenoic acid levels were significantly inversely associated with aggregation but the difference between the relationship at diagnosis and after three months was not statistically significant. The association between platelet omega 3 fatty acids and platelet aggregation suggest that dietary change aimed at increasing the proportions of these fatty acids might favourably influence vascular disease in NIDDM via an effect on platelet function.

Adult↗

Evolution of a terminal deoxynucleotidyl transferase-positive lymphoma from a chronic T cell lymphocytosis.

A 56-yr-old Caucasian man presented with a generalised scaly rash and a peripheral blood lymphocytosis of 5.6 X 10(9)/l. 5 yr later he developed cutaneous nodules, lymphadenopathy and hepatosplenomegaly. Cells with convoluted nuclei and prominent nucleoli were seen in the peripheral blood. He underwent splenectomy and received intensive chemotherapy but died 6 months later with CNS infiltration. At presentation the peripheral blood lymphocytes were E-ve, UCHT1 + ve, and OKT8 + ve. Following transformation, cells in blood, spleen and CSF were E-ve, OKT11 + ve, DR + ve and Tdt + ve. A proportion of these cells had a Sézary-like appearance at E/M. The splenic cells showed functional suppressor activity. This is the first reported case of the evolution of a Tdt + ve lymphoma from a post-thymic T cell lymphocytosis.

DNA Nucleotidylexotransferase↗

Comparison of the effects of gastric antisecretory agents in healthy volunteers and patients with duodenal ulcer.

Thirty published studies of the clinical pharmacology of gastric antisecretory agents in normal volunteers and duodenal ulcer patients were reviewed. The aim was to investigate the relationship between antisecretory effect in the two populations. There was a significant correlation between effect in patients and normal subjects for suppression of 24 hour intragastric acidity (r = 0.732; p = 0.0068), nocturnal intragastric acidity (r = 0.861; p = 0.0033) and nocturnal acid output (r = 0.964; p = 0.0069). The regression lines for 24 hour and nocturnal acidity were very similar. The expected antisecretory effect of a particular dosage regimen in patients with duodenal ulcer can be predicted mathematically from data derived from studies in normal volunteers.

Anti-Ulcer Agents↗

The correlation between acid suppression and peptic ulcer healing.

Suppression of gastric acid forms the basis of treatment of duodenal and gastric ulcer, but the precise relationship between suppression of acidity and healing rates has not been defined. We examined the results of controlled trials and clinical pharmacological studies of 24-h intragastric acidity involving antisecretory agents. Data on 24-h and nocturnal hydrogen ion activity and nocturnal acid output were obtained, and the healing rates in duodenal ulcer were calculated. Duodenal ulcer healing rates after 4 weeks showed a significant correlation with suppression of 24-hour hydrogen ion activity (r = 0.63; P less than 0.05), and a highly significant correlation between healing and the suppression of nocturnal hydrogen ion activity (r = 0.93; P less than 0.0001). Nocturnal acid output was not significantly correlated. For gastric ulcer, no such association was seen for suppression of either 24-hour or nocturnal hydrogen ion activity. Duodenal ulcer is regarded as an acid-related disorder, but in gastric ulcer other factors may be more important in pathogenesis and treatment.

Anti-Ulcer Agents↗

Antibodies to shared idiotypes as agents for analysis and therapy for human B cell tumors.

Monoclonal anti-idiotypic antibodies generated against idiotypic immunoglobulin (Ig) of neoplastic B lymphocytes can be selected from growing hybridoma clones by their ability to recognize idiotypic but not normal IgM. This group of antibodies can be subdivided into those that bind to the target tumor cells in the presence of normal human serum (approximately 85% of the clones) and those in which binding is inhibited by serum (approximately 15%). The former appear to be specific for private idiotypic determinants whereas the latter recognize cross-reacting idiotypic determinants. Such cross-reactivity is reflected both in recognition of a small percentage of normal Ig and also in binding to other lymphomas. The anti-idiotypes specific for private determinants can be used for therapy, with only idiotypic Ig secreted by tumor cells able to block its access to cells. The cross-reacting anti-idiotypes will face in addition the barrier of the proportion of normal Ig with which it reacts. The attraction of using a single monoclonal reagent for more than one patient has led us to develop an assay that measures the level of such blocking and to propose that those recognizing less than 30 micrograms/mL of normal Ig could be placed in a panel for possible therapy for several patients; less restriction need apply to antibodies for monitoring tumor progress. The assay is described, and examples of such antibodies raised against lymphoma cells from two patients are given together with comparisons with them of anti-idiotypes specific for private determinants.

Aged↗

Increased arachidonic acid level in diabetic platelets following improvement in diabetic control.

A group of non-insulin dependent diabetics taking oral hypoglycaemic therapy were studied to determine the effect of improved diabetic control on the platelet levels of the prostaglandin precursor fatty acids. The patients were randomised to receive either a low carbohydrate diet (35% of total energy) for six weeks or a high carbohydrate diet (55% of total energy), high fibre diet for six weeks and the diets were then reversed. At the end of the high carbohydrate, high fibre diet the mean fasting blood glucose (6.6 mmol section 1) and mean percentage glycosylated haemoglobin (8.2%) were significantly lower than after the low carbohydrate diet (7.8. mmol/l, p less than 0.05: 9.9%, p less than 0.01). Mean platelet phospholipid arachidonic acid percentage was significantly higher after the high carbohydrate, high fibre diet (24.2%) than after the low carbohydrate diet (19.9%, p less than 0.01). There were no significant changes in the other platelet fatty acids.

Aged↗

Primary cerebral lymphoma. A histologic and immunohistochemical study of six cases.

Between 1981 and 1985, three male and three female patients (age range, 26 to 65 years) with primary central nervous system lymphoma underwent biopsy procedures and were treated in the Wessex Neurological Centre, Southampton, United Kingdom. The primary nature of the disease was confirmed by extensive clinical and radiologic investigation, and a combined approach of cytologic, histologic, and immunohistochemical studies contributed to the diagnosis and characterization of these tumors. By the Kiel classification, the lesions included five diffuse follicle center cell lymphomas and one T-cell lymphoma. Five of the lesions were present in the cerebral hemispheres, and three of these were multifocal. Only one patient presented with a lesion in the posterior fossa. Despite combinations of surgery, radiotherapy, and chemotherapy, all patients died, the longest postoperative survival being two years.

Aged↗

Effect of hypoxia on oxidative and reductive pathways of omeprazole metabolism by the isolated perfused rat liver.

The effect of hypoxia on the elimination of omeprazole, a potent inhibitor of gastric acid secretion, was studied in the isolated perfused rat liver. During normal oxygenation, a 10 mg bolus dose was eliminated rapidly (T 1/2 beta = 8.0 +/- 1.1 min; mean +/- S.E.M., N = 4), while under hypoxic conditions T 1/2 beta was increased to 81.6 +/- 5.4 min (P less than 0.01). Upon reoxygenation, T 1/2 beta returned to 9.6 +/- 1.3 min. During hypoxia, perfusate concentrations of an oxidative metabolite (the sulphone) were reduced by 68%, while those of the reductively-generated sulphide increased 4-fold. With reoxygenation, both formation and elimination of the sulphone were increased, while the sulphide, which had accumulated during the hypoxic period, was eliminated rapidly. These findings were duplicated in steady-state experiments, in which omeprazole clearance during hypoxia fell by at least 70%, and sulphide concentrations in perfusate rose from undetectable levels to 200 ng/ml (at least a 10-fold increase). Sulphone concentrations did not change with hypoxia, consistent with a reduction in both its formation and elimination rates. We conclude that the hepatic elimination of omeprazole is severely retarded by hypoxia, but that this effect is promptly reversed by reoxygenation. The increased formation of reductive metabolite during hypoxia is not of sufficient magnitude to sustain the normal hepatic elimination of omeprazole.

Animals↗

Paget's disease of the nipple. Immunohistochemical localization of milk fat globule membrane antigens.

The authors have used the indirect immunoperoxidase technique to examine the presence and distribution of milk fat globule membrane antigens in 12 cases of mammary Paget's disease using two monoclonal antibodies, HMFG-1 and HMFG-2. These stain breast epithelial cells but do not stain normal epidermis. The Paget's cells showed a similar pattern of cytoplasmic staining to that seen in the underlying intraduct or invasive carcinoma, therefore confirming them to be malignant ductal cells. To support this one of the cases was stained with the antibody LE 61 which is specific for nonepidermal epithelial cytokeratins. The result was strongly positive in Paget's cells in the epidermis but not in squamous cells.

Antibodies, Monoclonal↗

Variation in natural killer activity in peripheral blood during the menstrual cycle.

Natural killer activity was measured sequentially in normal female volunteers through their menstrual cycle. During the periovulatory period there was a significant fall in natural killer activity compared with in normal male volunteers. This variation was not apparent in women taking oral contraception. Cytotoxic activity was not related to oestradiol concentrations in individual women. The data support an interaction between immunological activity and sex hormones over the normal physiological range and would account for the described reduction in natural killer activity in pooled blood from female blood donors.

Adult↗