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Biomedical subjects

D H Jones

Publications and source records attributed to D H Jones.

At least 181 records · Page 10Linked to original sources
PubMed1984

Acute exposure to hymenoxon: electron microscopic study of the mouse liver.

Young, male mice (25 to 30 g) were given oral doses of hymenoxon, a sesquiterpene lactone, for 5, 10, or 20 days. Hymenoxon, isolated from Hymenoxys odorata DC, was dissolved in dimethyl sulfoxide (DMSO) and water (1:1, v/v) and was administered daily at a dosage level of 100 mg/kg of body weight for 5, 10, or 20 days. Two control groups were maintained; 1 group was given DMSO and water, and 1 group was given water only. Twenty-four hours after the last dosing, the mice were euthanatized and their livers were processed for transmission electron microscopy. Hepatocyte organelles of hymenoxon-treated mice appeared normal although the bile canaliculi contained a fine granular material and membranous structures, including myelin figures. The canaliculi of hymenoxon-treated mice were also markedly dilated, compared with bile canaliculi in the control groups. The mean area of bile canaliculi of the 5-, 10-, and 20-day mice was 14.08 microns2, 15.65 microns2, and 17.56 microns2, respectively, compared with 7.73 microns2 for the canaliculi of DMSO + water-treated mice. The P values were less than 0.001, 0.02, and 0.05 for the 5-, 10-, and 20-day hymenoxon-treated mice, respectively. Seemingly, the mouse was not a good model for studying hepatic ultrastructural changes produced by hymenoxon, using dosages less than or equal to 100 mg/kg/day for 20 days.

Animals↗
PubMed1983

An ELISA to detect monoclonal antibodies specific for lipid determinants of Mycoplasma pneumoniae.

An enzyme-linked immunosorbent assay (ELISA) was developed for analysis of monoclonal antibodies directed towards lipid determinants of Mycoplasma pneumoniae. Chloroform-methanol lipid extracts as well as chromatographed lipid fractions of M. pneumoniae were bound to polyvinylchloride microtiter wells. Of 293 clones positive to M. pneumoniae as detected by a whole cell ELISA, a total of 78 clones produced antibodies which selectively bound to lipid extracts of M. pneumoniae. The simplicity and reproducibility of the assay permit rapid screening for detection of antibodies directed against non-protein cellular antigens.

Animals↗
PubMed1983

Binding and uptake of concanavalin A into rat brain synaptosomes: evidence for synaptic vesicle recycling.

The specific binding of radioiodinated concanavalin A (125I-con A) to rat brain synaptosomes was shown to be saturable. In the presence of excess on A binding was rapid and was completed within 5 min (t1/2 was 25 s) at 37 degrees C, and at saturation the amount bound did not change over time. Under the electron microscope, concanavalin A-ferritin (con A-ft) bound to synaptosomes in two regions: in the extra-junctional plasma membrane and within the synaptic cleft of Gray type 1 and 2 synapses. Synaptosomes incubated with con A-ft at 37 degrees C internalized bound lectin by endocytosis through coated pits. Endocytosis took place in the extra-junctional membrane, because it can occur before con A-ft has penetrated into the synaptic cleft, and continued for a considerable time (more than 30 min) after saturation of the receptor(s). Synaptic vesicles, which have at least two con A receptors on the internal aspect of their membranes, and cisternae, become labelled. When exocytosis was induced in synaptosomes by K+ depolarizations, synaptic vesicle con A receptors became incorporated into the plasma membrane and were labelled with 125I-con A causing a 2.5-fold increase in con A binding that was Ca2+ dependent. These experiments thus provide evidence for the transient incorporation of synaptic vesicle membrane glycoproteins into the plasma membrane during transmitter release.

Animals↗
PubMed1983

Role of venous sampling in locating a phaeochromocytoma.

Selective venous sampling was performed in 31 patients in whom the diagnosis of phaeochromocytoma was suspected on clinical and biochemical grounds. Data from samples assayed for their adrenaline and noradrenaline content using a radioenzymatic technique were used to confirm or refute the suspected diagnosis. In 19 of the 31 patients a phaeochromocytoma was subsequently removed surgically, and the remaining 12 patients are now thought not to have tumours (mean follow up period: four years). Analysis of the assay data shows that selective venous sampling correctly identified the presence of a tumour in all 19 patients, and correctly excluded the diagnosis in 11 of the 12 remaining patients--an overall success rate of 97%. Success rates of 88% for arteriography and 84% for computed tomography were recorded, though these investigations were not performed in all patients. Ultrasound and intravenous urography were much less accurate. On the basis of this study a sequence of investigation is proposed for patients with a suspected phaeochromocytoma. Computed tomography occupies a central role in this sequence with venous sampling (and occasionally other techniques) being used only as complementary investigations when specific indications for their use exist.

Adolescent↗
PubMed1983

Sporidesmin toxicity in rabbits: biochemical and morphological changes.

The earliest lesion in rabbits dosed orally with 2 mg of sporidesmin per kg of body weight was necrosis of occasional hepatocytes 1 day after dosing. The most consistent lesion was a severe necrotizing cholangitis of medium and large-sized intrahepatic and extrahepatic bile ducts, first seen 2 days after dosing. Similar lesions were also present in the gall bladder of some rabbits. Expansion of portal triads with fibrous tissue and proliferating bile ductules progressed to pseudo-lobulation by 21 days. Other hepatic changes observed irregularly included large infarcts at the periphery of some lobes, and multiple small foci of coagulation necrosis in midzonal and periportal regions. Vascular necrosis and thrombosis, invariably adjacent to necrotic bile ducts, was presumably responsible for the hepatic necrosis. Serum cholesterol and total bilirubin concentrations and GGT activity reached peaks 15 days after dosing and were useful indicators of the severity of biliary lesions. Serum ID activity was the most useful indicator of hepatic necrosis following oral dosing with sporidesmin. The similarity between hepatobiliary lesions observed in sheep and rabbits with experimental sporidesmin toxicity suggests that the rabbit would be a useful model for studying methods of treatment and prevention of "facial eczema" in ruminants.

Animals↗
PubMed1983

The role of dexamethasone in the modification of misonidazole pharmacokinetics.

A review of misonidazole pharmacokinetics in 83 consecutive patients treated for tumours other than glioma has shown that among patients not receiving enzyme-inducing agents the plasma elimination half life is lower in patients taking steroids. Such a difference is not seen if patients already taking enzyme inducers are given steroids. Five further patients with carcinoma of the lung, treated with radiation over a period of 3 weeks, have been studied in greater detail. Misonidazole, in oral dose of 1 gm-2, was given in conjunction with the first and last radiotherapy fractions, and dexamethasone, in a divided daily dose of 8 mg, was given throughout the radiation treatment, commencing after the first treatment. Misonidazole pharmacokinetics were studied at each administration. Following the dexamethasone treatment period there was a 25% reduction in misonidazole plasma elimination half life, a 24% reduction in plasma AUC0-00, and a 38% increase in 24 h urinary excretion (all changes being statistically significant--P less than 0.005). No changes were observed in the plasma AUC0-24 and urinary excretion of the major metabolite desmethylmisonidazole. Glomerular filtration rates in one patient, before and after treatment with dexamethasone, remained unchanged. These results suggest that the effect of dexamethasone on misonidazole kinetics is not related to an enhancement of demethylation.

Adult↗
PubMed1983

Human lymphoblastoid interferon in the treatment of small cell lung cancer.

Ten patients with small cell lung cancer were treated with high dose human lymphoblastoid interferon (50-100 megaunits m-2) for 5 days, followed by low dose interferon (3 megaunits m-2) for 3 weeks. At the end of treatment, and one month later, there was no evidence of either complete or partial response. The treatment produced fever, anorexia and weight loss, with transient leucopenia and thrombocytopenia; there was evidence of a non-cholestatic elevation of serum alanine aminotransferase, with clinical deterioration in the condition of three patients presenting with hyponatraemia. A transient hypocalcaemia during high dose therapy was also noted. It seems that lymphoblastoid interferon as a single agent is unlikely to have a role in the treatment of small cell lung cancer, and that its administration as employed in this study is associated with considerable toxicity.

Aged↗
PubMed1983

A dose-response study of I3-cis-retinoic acid in acne vulgaris.

13-cis-retinoic acid has been used as a single agent in the treatment of seventy-six patients with previously unresponsive cystonodular acne. The study was carried out in a double-blind fashion using three doses of the drug. Ninety per cent of the patients responded with a 70% improvement in the acne severity. Sixty-six per cent of the patients experienced no further problems with their acne during follow-up. Side-effects were frequent. The 0.5 mg/kg b.w. dose is recommended for the initial course of treatment.

Acne Vulgaris↗
PubMed1983

The penetration of misonidazole and desmethylmisonidazole into brain tumours and other central nervous system tissues in man.

The concentration of drug after oral administration of 1 g misonidazole to patients undergoing neurosurgery has been studied in samples taken from intracerebral tumours, normal brain, cerebrospinal fluid and brain tumour cyst fluid. A total of 31 patients yielded samples at various times 2-8 h after drug administration. Results show a considerable range of tumour/plasma percentages but from about 2-5 h after drug administration this averaged between 65-80%. Normal brain and CSF showed similar good penetration but drug entry into cyst fluid was lower (30-50%). A further study with desmethylmisonidazole given to 11 additional patients showed a similar range of tumour penetration but lower concentrations in CSF and cyst fluid (10-20%). Low values were also seen in some but not all of the normal brain tissue samples. Necrotic tumour also had much lower concentrations than macroscopically viable tissue. These results are discussed in terms of their clinical relevance to sensitiser studies on patients with brain tumours with drugs of different lipophilicities.

Adolescent↗
PubMed1983

The role of microsomal enzyme inducers in the reduction of misonidazole neurotoxicity.

In a series of studies, we have shown that phenytoin, 300 mg daily for one week, produces consistent hepatic microsomal enzyme induction, resulting in a decrease of 25% in misonidazole half-life, without causing any toxicity per se. A longer period of administration gives only a slightly greater induction. Phenobarbitone in a daily dose of 90 mg causes a reduction of 18% and 23% in misonidazole half-life after 1 and 2 weeks' pre-treatment respectively, but is less suitable clinically because of its sedative effect. A further series of studies using phenytoin as the inducing agent has shown that, despite adequate enzyme induction and increased misonidazole metabolism, it is impossible to increase the total dose of misonidazole beyond the usually accepted value of 12 g/m2 because of unacceptable neuropathy (a rate of 50% at a dose of 14 g/m2 over three weeks). In single doses of above 3.0-4.0 g of misonidazole, severe nausea and vomiting are prominent, so that this side effect is a determining factor in the treatment fractionation. Audiometric studies show no correlation between the incidence of peripheral neuropathy and abnormal audiograms, and have no value in the early prediction of neurotoxicity. It seems that despite causing increased metabolism, enzyme induction does not protect against neurotoxicity and thus will not permit the use of higher doses of misonidazole for increased radiosensitisation.

Adult↗
PubMed1983

Amoscanate as a topically applied chemical for prophylaxis against Schistosoma mansoni infections in mice.

Amoscanate (0.1% w/v) in methanol solution applied to skin by tail immersion 1 day prior to cercarial exposure provided mice with better than 90% protection against mature Schistosoma mansoni infections. Cercariae penetrated and schistosomula migrated from treated skins as readily as in control skins. Lung incubation assays, however, indicated that day 7 lung worm burdens were only about half those of control values. By day 20, worm burdens were reduced further to approximately 15% of those for control mice. The delayed prophylactic activity was apparently not due to percutaneously absorbed compound. Wipe application of amoscanate to the skin was nearly as effective as immersion.

Administration, Topical↗
PubMed1983

Increased expression of human monocyte HLA-DR antigens and Fc gamma receptors in response to human interferon in vivo.

The expression of class II MHC encoded antigens (HLA-DR) and Fc gamma receptors by peripheral blood monocytes from untreated patients with small cell carcinoma of the bronchus was compared with that of normal donors. Fc gamma receptor expression was found to be elevated in these patients in comparison with normal. In contrast HLA-DR antigen expression by patients' monocytes was somewhat depressed in comparison with normal. Continuous intravenous infusion of a total of 400 megaunits/m2 of human lymphoblastoid interferon-alpha (IFN-alpha) over a 5 day period markedly increased both monocyte HLA-DR antigen expression and Fc gamma receptor expression in comparison with that of untreated patients and normal donors. The initial increases declined somewhat but were still evident after 3 weeks of intermittent intramuscular IFN-alpha therapy.

Antibody Formation↗
PubMed1982

Microcomputer system in an accident unit.

A microcomputer-based records system has been developed for use in the accident unit of a district general hospital. Patient details are entered directly at the reception desk and the computer generates a casualty card that is updated after the patient has been seen by the doctor, who determines the diagnosis to be recorded and specifies the injury coding. Information is stored on floppy discs, each holding the details of 3400 patients. The computer is used to produce a daily log-book of attendances, including revisits. The stored data may be examined and analysed for both administrative and medical purposes. The work load can be rapidly analysed according to various options that include the nature, type, and site of injuries. The system was introduced in December 1980. Location within the unit allows control over its operation, and many of the limitations of a manual system have been overcome.

Computers↗
PubMed1982

A double-blind study of the effects of 13-cis-retinoic acid on acne, sebum excretion rate and microbial population.

Forty-eight acne patients were treated orally with 13-cis-retinoic acid in a double-blind dose response study. There was a marked clinical improvement with a concomitant reduction in sebum excretion rate (SER) and production rate of free fatty acids (FFA). Microbial numbers decreased significantly; the decrease in propionibacteria was greater than that of aerobic bacteria. The decline in micro-organisms occurred after the reduction in sebum and FFA production. This suggests that the effect of the drug upon micro-organisms is secondary to the change in sebum excretion but it is nevertheless an important factor in the resolution of the acne.

Acne Vulgaris↗