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Biomedical subjects

C James

Publications and source records attributed to C James.

At least 145 records · Page 8Linked to original sources
PubMed1987

Are iron-folate supplements harmful?

Zinc absorption during pregnancy was measured before and 24 h after 2 wk of daily, oral, iron-folate supplements. Absorption was reduced 24 h after iron-folate, which suggests a mucosal rather than a luminal effect. Also, zinc absorption in 10 healthy volunteers was reduced by folate supplements alone. Therefore, routine iron and folate supplementation may both have deleterious effects on zinc metabolism, especially during pregnancy when iron-folate supplements are often prescribed despite adequate dietary intakes of iron and folate but not of zinc.

Adult↗
PubMed1986

Control of glycogen synthase by insulin and isoproterenol in rat adipocytes. Changes in the distribution of phosphate in the synthase subunit in response to insulin and beta-adrenergic receptor activation.

Rat adipocytes were incubated with [32P]phosphate to label glycogen synthase, which was rapidly immunoprecipitated from cellular extracts and cleaved using either CNBr or trypsin. All of the [32P]phosphate in synthase was recovered in two CNBr fragments, denoted CB-1 and CB-2. Isoproterenol (1 microM) rapidly decreased the synthase activity ratio (-glucose-6-P/+glucose-6-P) and stimulated the phosphorylation of both CB-1 and CB-2 by approximately 30%. Insulin opposed the decrease in activity ratio and blocked the stimulation of phosphorylation by isoproterenol. Incubating cells with insulin alone changed the 32P content of neither CB-1 nor CB-2. Trypsin fragments were separated by reverse phase liquid chromatography and divided into peak fractions, denoted F-I-F-VII in order of increasing hydrophobicity. F-V contained almost half of the [32P]phosphate and was phosphorylated when synthase was immunoprecipitated from unlabeled fat cells and incubated with [gamma-32P]ATP and the cAMP-independent protein kinase, FA/GSK-3. That F-V also had the same retention time as the skeletal muscle synthase fragment containing sites 3(a + b + c) suggests that it contains sites 3. Muscle sites 1a, 5, 1b, and 2 eluted with F-I, F-II, F-VI, and F-VII, respectively. F-V was increased approximately 25% by isoproterenol, but the largest relative increases were observed in F-I (4-fold), F-III (4-fold), and F-VI (2-fold). These results indicate that beta-adrenergic receptor activation results in increased phosphorylation of multiple sites on glycogen synthase. Insulin plus glucose decreased the overall 32P content of synthase by approximately 30%, with the largest decrease (40%) occurring in F-V. Without glucose, insulin decreased the [32P]phosphate in F-V by 17%, an effect which was balanced by increases in F-I, F-II, and F-III so that no net change in the total 32P contents of the fractions was observed. Thus, activation of glycogen synthase by the glucose transport-independent pathway seems to involve a redistribution of phosphate in the synthase subunit.

Adipose Tissue↗
PubMed1985

A phase II study of ifosfamide in children with recurrent solid tumours.

Twenty children with recurrent or unresponsive tumours (10 Wilms', 3 rhabdomyosarcoma, 4 Ewings's, 1 osteosarcoma, 1 hepatoblastoma, 1 hepatoma) and one untreated patient with renal carcinoma were given ifosfamide as a 24-h infusion (5 mg/m2), with mesna as uroprotective. The number of courses ranged from 1 to 13 (median 3), and the interval between them was 2-3 weeks. Sixteen of these patients had previously received cyclophosphamide. Complete clinical responses were seen in 3 cases (2 Wilms' and 1 Ewing's) and lasted 5, 7, and 9 months. Partial responses were seen in 3 instances, mixed response or stable disease in 4, and progressive disease in 11. Treatment was well tolerated in most patients, with no cystitis or severe myelosuppression, but 2 children developed transient neurological symptoms and 1 became hypertensive. Nausea and vomiting were controlled by high-dose dexamethasone in most children. Plasma ifosfamide levels were estimated by means of gas-liquid chromatography in 10 patients. Peak concentrations ranged from 38 to 125 micrograms/ml (median 80). The elimination half-life, at 2.5-5.2 h (median 3.2) was shorter than previously reported in adults. Future studies should test the possibility that ifosfamide-containing combination chemotherapy may be more effective than the regimens, usually including cyclophosphamide, that are currently used as front-line treatment of embryonal and Ewing's sarcoma.

Adolescent↗
PubMed1984

Activation of glycogen synthase by insulin in rat adipocytes. Evidence of hormonal stimulation of multisite dephosphorylation by glucose transport-dependent and -independent pathways.

Adipocytes were incubated with [32P]phosphate to achieve steady state labeling of glycogen synthase. The enzyme was then rapidly immunoprecipitated and subjected to electrophoresis on polyacrylamide slab gels in the presence of sodium dodecyl sulfate. The 32P-labeled glycogen synthase had an apparent molecular weight ( Mapp ) equal to 90,000. All of the [32P]phosphate could be recovered in two cyanogen bromide fragments. The larger fragment, CB-2 ( Mapp = 28,000), contained about five times more [32P]phosphate than the smaller fragment, CB-1 ( Mapp = 15,500). Insulin increased the activity ratio (-glucose-6-P/+glucose-6-P) of glycogen synthase from 0.12 to 0.26, but did not decrease the amount of [32P]phosphate in the enzyme. However, insulin promoted the formation of species of CB-2 of lower Mapp , suggesting dephosphorylation of sites that affected the electrophoretic mobility of the fragment. Glucose did not affect the mobility of CB-2, but slightly increased the activity ratio and decreased the [32P] phosphate by approximately 20%. With insulin plus glucose, the increase in activity ratio was much greater than the additive effects of either agent alone. The combination decreased the [32P]phosphate in each cyanogen bromide fragment by approximately 60%, indicating that the synergistic activation was due to enhanced dephosphorylation of multiple sites. 2-Deoxyglucose also promoted dephosphorylation of glycogen synthase, decreasing the 32P content of CB-1 and CB-2 by approximately 40% each. 3-O-Methylglucose was without effect. The results presented suggest that the activation of glycogen synthase by insulin via a glucose transport-dependent pathway may involve increased intracellular glucose-6-P which promotes dephosphorylation of sites in both CB-1 and CB-2. Activation by a glucose transport-independent pathway appears to be confined to sites located in CB-2.

3-O-Methylglucose↗
PubMed1984

Control of phosphorylase in cultured rat skeletal muscle cells. Changes in synthesis and degradation resulting from differentiation and muscle activity.

The control of phosphorylase levels was investigated in rat skeletal muscle cells developing in vitro. The amount of enzyme was directly measured after immunoprecipitation using specific antibodies. The rate of phosphorylase synthesis was estimated by measuring the initial rate of formation of [3H]phosphorylase after incubating cells with [3H]tyrosine. Rates of degradation were determined either from pulse-chase experiments using [3H]tyrosine or by the loss of enzymatic activity following inhibition of protein synthesis. A large increase in phosphorylase occurred at the time myoblasts were fusing into myotubes. The accumulation of enzyme was preceded by a marked increase in the synthetic rate and was associated with a severalfold increase in the half-life of the enzyme. Following fusion, the myotubes began to spontaneously contract, and shortly thereafter, decreases in both the half-life and amount of phosphorylase were observed. The paralytic agents tetrodotoxin and lidocaine were without effect on phosphorylase levels before the onset of spontaneous activity; however, both agents increased the amount of enzyme when added to contracting myotubes. Tetrodotoxin had little effect on synthesis of [3H]phosphorylase but doubled the half-life of the enzyme. These and other results indicate that the increase in phosphorylase in differentiating muscle cells results from the coordinate control of both its synthesis and degradation, and that muscle activity decreases phosphorylase by increasing its degradation.

Animals↗
PubMed1984

Prevalence of acute conjunctivitis caused by chlamydia, adenovirus, and herpes simplex virus in an ophthalmic casualty department.

The causes of acute conjunctivitis in 140 consecutive patients attending an ophthalmic casualty department in London were investigated. Laboratory evidence of infection with Chlamydia trachomatis, adenovirus, or herpes simplex virus was found in 52 (37%) cases. In 70 cases (50%) no evidence of infection with these agents was found. In the remaining 18 cases (13%) laboratory results were inconclusive. The importance of these findings, the role of laboratory investigations in the differential diagnosis of acute conjunctivitis, and their cost-benefit are discussed.

Acute Disease↗
PubMed1983

Long-term infection of Schistosoma mansoni in a vervet monkey (Cercopithecus aethiops).

Schistosoma mansoni infection in Cercopithecus species monkeys has been previously monitored for up to five years. This is an account of observations made during an autopsy on a male vervet monkey which had harboured the parasite for 15 years. Viable eggs had been recovered from the faeces throughout the infection, being hatched to observe the emergence of miracidia. Apart from a nodular appearance of the liver capsule, which was noted before the perfusion, and localized haemorrhaging in the large bowel there was comparatively little pathology attributable to the parasite. 86 worms were recovered from the mesenteries by perfusion. The distribution of worm eggs in the tissues was mainly in these two organs, although with the remarkably low incidence of granuloma it is likely that the schistosome infection would have been overlooked in a routine autopsy. It is stressed that these observations have been made on an individual animal, but it is felt that there is real significance with respect to the aetiology of natural transmission.

Animals↗
PubMed1982

Schistosoma haematobium in the baboon (Papio anubis): effect of vaccination with irradiated larvae on the subsequent infection with percutaneously applied cercariae.

Groups of five baboons were vaccinated three times at approximately six-weekly intervals at a rate of 1,000 organisms per kg of gamma-irradiated Schistosoma haematobium larvae. Five vaccines were tested: 3 and 20 Krad cercariae applied percutaneously; fresh 3 and 20 Krad mechanically transformed schistosomula injected intramuscularly; and cryopreserved 20 Krad schistosomula injected intramuscularly. These five groups and an unvaccinated control group were challenged percutaneously with 7,500 S. haematobium cercariae three months after the last vaccination. The efficacy of the vaccines was judged by faecal egg excretion, and by adult worm and tissue egg recoveries at necropsy 4.5 months after challenge. Significant protection, with 64 to 89% reductions in worm burden and parallel reductions in egg production, was achieved by all but the cryopreserved vaccine, although egg production was not significantly reduced in those female worms which did mature. Cercariae tended to give more protection than schistosomula and 20 Krad more protection than 3 Krad. No significant pathology could be detected in an additional baboon vaccinated with 20 Krad schistosomula but not challenged with cercariae. This is an encouraging result for the development of a live vaccine against S. haematobium.

Animals↗
PubMed1982

Immunological cross-reactivity of enterotoxins of Aeromonas hydrophila and cholera toxin.

Pre-incubation with anticholera toxin (ACT) significantly reduced intestinal secretion induced by cell-free broth preparations of heat-labile toxins (LT) of Escherichia coli and Aeromonas hydrophila in jejunal perfusion experiments in rats in vivo. Pre-incubation with ACT also prevented cytotoxicity by E. coli LT in the Y1 cell culture system. Pre-incubation had no effect on cytotoxicity in Y1 and L132 cell lines or on haemolytic activity with cell-free preparations of A. hydrophila. In another series of experiments rats were immunized with cholera toxin given as an intraperitoneal priming dose followed 12 days later by intraduodenal boosting. Immunization significantly protected against net intestinal fluid secretion induced by enterotoxigenic E. coli and A. hydrophila and by cholera toxin.

Aeromonas↗
PubMed1981

The enzyme linked immunosorbent assay (ELISA) for the determination of circulating antigen and antibody in Schistosoma haematobium-infected baboons.

The ELISA was used to measure circulating antigen and antibody in four baboons of which three were treated. The circulating antigen appeared earlier after infection than the antibody which eventually, however, reached a higher level. Both antigen and antibody levels increased slightly after treatment and thereafter declined to reach background levels eight weeks later. It is concluded that the ELISA has a potentially useful role in detecting both antibody and circulating antigen and that it may be successfully used in evaluating the efficacy of schistosomicides.

Animals↗
PubMed1981

The effect of praziquantel on Schistosoma haematobium, S. japonicum and S. mansoni in primates.

Baboons infected with S. haematobium and vervet monkeys infected with S. japonicum were treated orally with different dosage regimens of 2-cyclohexylcarbonyl-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinolin-4-on e(praziquantel, EMBAY 8440, Biltricide) and were autopsied and perfused 3--4 months after treatment. The results suggest that a single oral dose of 75--100 mg/kg body weight is likely to be effective against S. haematobium in the baboon. Female worms of S. haematobium are apparently more susceptible to the compound than male worms. The classic hepatic shift of adult schistosomes was observed in all the primates, but histopathological studies showed that numerous worms also died in situ, only a few being found in the lungs. The results obtained with praziquantel against S. japonicum in the vervet monkey show that a complete cure was obtained in the animal given 50 mg/kg on five consecutive days. A predominant characteristic in the pathology of the animals given a curative dose of praziquantel was the total resolution of cellular reaction and fibrosis in the tissues containing known numbers of dead residual eggs. In the baboons infected with S. haematobium, the ureters and bladders had recovered their functional integrity and in the vervet monkeys infected with S. japonicum, a similar resolution of pathology in the liver and bowel was apparent.

Animals↗
PubMed1980

Effect of Schistosoma haematobium and N-butyl-N-(4-hydroxybutyl)nitrosamine on the development of urothelial neoplasia in the baboon.

Experiments were conducted to determine whether bladder cancer would develop in primates (Papio sp.) infected with S. haematobium and concurrently exposed to low initiating doses of the bladder carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). To control for the systemic effects of schistosomiasis, 5 baboons were infected with S. mansoni, which does not lay its eggs in the bladder wall; to control for the effect of the carcinogen alone, 5 others were treated with BBN alone at the rate of 5 or 50 mg/kg per week for the duration of the experiment. Five animals were infected with S. haematobium and had no further treatment, and the main experimental group of 10 baboons was infected with S. haematobium and also treated weekly with 5 mg/kg BBN for up to 2½ years. Four of the 10 animals in the last group, but none in the three control groups developed neoplastic disease of the urothelium. Four animals with S. haematobium plus BBN treatment developed in situ carcinoma in the bladder (3 latent adenomatous lesions and 1 more advanced papillary tumour) and 2 of these animals plus 1 other had slightly dysplastic urothelial endophytic papillary growths of the ureter which penetrated the muscle layer. By contrast, none of the control animals developed urothelial carcinomas, though 4/5 of those with S. haematobium infection alone had inflamed bladders with polypoid lesions, and one individual had endophytic papillary hyperplasia of the ureter. The animals were killed after 2½ years while still relatively immature or adolescent, and it is possible that had they been allowed to survive longer some of the BBN-only group would have developed bladder cancer, and more of the latent lesions seen in the BBN + schistosomiasis group would have progressed to invasive carcinoma. It is postulated that, in this model for human bilharzial bladder cancer, schistosomiasis supplies the proliferative stimulus necessary to accelerate cancer growth from latent tumour foci produced by exposure to low doses of the bladder carcinogen. In areas of endemic schistosomiasis, carcinogenesis might be initiated, for example, by low doses of nitrosamines produced in the urinary tract during bouts of bacteriuria.

Animals↗