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Biomedical subjects

J Fuller

Publications and source records attributed to J Fuller.

At least 55 records · Page 3Linked to original sources
PubMed1998

Endotoxin and cytokines increase hepatic sphingolipid biosynthesis and produce lipoproteins enriched in ceramides and sphingomyelin.

Alterations in triglyceride and cholesterol metabolism often accompany inflammatory diseases and infections. We studied the effects of endotoxin (lipopolysaccharide [LPS]) and cytokines on hepatic sphingolipid synthesis, activity of serine palmitoyltransferase (SPT), the first and rate-limiting enzyme in sphingolipid synthesis, and lipoprotein sphingolipid content in Syrian hamsters. Administration of LPS induced a 2-fold increase in hepatic SPT activity. The increase in activity first occurred at 16 hours, peaked at 24 hours, and was sustained for at least 48 hours. Low doses of LPS produced maximal increases in SPT activity, with half-maximal effect seen at approximately 0.3 microg LPS/100 g body weight. LPS increased hepatic SPT mRNA levels 2-fold, suggesting that the increase in SPT activity was due to an increase in SPT mRNA. LPS treatment also produced 75% and 2.5-fold increases in hepatic sphingomyelin and ceramide synthesis, respectively. Many of the metabolic effects of LPS are mediated by cytokines. Interleukin 1 (IL-1), but not tumor necrosis factor, increased both SPT activity and mRNA levels in the liver of intact animals, whereas both IL-1 and tumor necrosis factor increased SPT mRNA levels in HepG2 cells. IL- produced a 3-fold increase in SPT mRNA in HepG2 cells, and the half-maximal dose was 2 ng/mL. IL-1 also increased the secretion of sphingolipids into the medium. Analysis of serum lipoprotein fractions demonstrated that very low density lipoprotein, intermediate density lipoprotein, and low density lipoprotein isolated from animals treated with LPS contained significantly higher amounts of ceramide, glucosylceramide, and sphingomyelin. Taken together, these results indicate that LPS and cytokines stimulate hepatic sphingolipid synthesis, which results in an altered structure of circulating lipoproteins and may promote atherogenesis.

Acyltransferases↗
PubMed1998

The London Academic Training Scheme (LATS): an evaluation.

BACKGROUND: A recognition of the inability of vocational training schemes (VTS) to teach all the skills needed for modern general practice, and the increasing unwillingness of vocationally trained doctors to commit to GP principal posts, has led to the promotion and piloting of post-VTS educational schemes. The London Academic Training Scheme (LATS) is a year's attachment to a University Department of General Practice in London, comprising seven academic and three clinical sessions. OBJECTIVE: We aimed to carry out an evaluation of the first 2 years of the LATS from the perspectives of the registrar, their departmental supervisor and the practice. METHODS: Data were collected by questionnaires, interviews and focus groups, at the beginning, during and at the end of the scheme. RESULTS: Results are available up to the midway point of the second (1996) intake. The registrars achieved confidence and success in research, with six publications in peer-referenced journals from the first cohort so far. Eight of this cohort were working in inner London 6 months later, seven in academic posts. The overwhelming career intention of the second cohort midway is to work in academic general practice in London. The registrars enjoyed their teaching opportunities and increased their confidence but would have liked more training and more time for teaching. All the supervisors identified positive effects on their departments, but some found the time commitment and the process of supervision challenging. Two out of the dozen practices involved with the first cohort had reservations about the attachment. The rest cited benefits in clinical care, involvement in research and time for their own development. CONCLUSION: The scheme fulfilled its immediate aims and is addressing the recruitment and retention of GPs in the inner city. Continuing follow-up is planned.

Education, Medical, Graduate↗
PubMed1997

Retinopathy and vision loss in insulin-dependent diabetes in Europe. The EURODIAB IDDM Complications Study.

PURPOSE: To assess the frequency of retinopathy and vision loss in patients with insulin-dependent diabetes mellitus and their relations to potentially modifiable risk factors. METHODS: The authors conducted a multicenter cross-sectional study of diabetic complications and their risk factors using standardized methods of assessment. The sample was comprised of 3250 insulin-dependent diabetic patients (1668 men, 1582 women) aged 15 to 60 years with mean (standard deviation) duration of diabetes of 14.7 (9.3) years from 31 European diabetes centers; 2991 of the patients were eligible for retinal photography. Visual acuity was measured using the Snellen chart. Retinopathy was evaluated by retinal photographs (two fields per eye) graded at a central facility. Glycated hemoglobin (HbA1c), cholesterol, triglyceride, fibrinogen, von Willebrand factor, and urinary albumin excretion rate were assessed at a single location. RESULTS: Corrected visual acuity was greater than or equal to 1.0 in both eyes in 69.7% of patients and less than or equal to 0.1 in the best eye in 2.3%. Factors significantly related to vision loss were age, duration of diabetes, glycated hemoglobin (HbA1c), and level of retinopathy. Mild nonproliferative retinopathy was found in 25.8% of the patients, moderate-severe nonproliferative retinopathy in 9.8% of the patients, and proliferative retinopathy in 10.6% of the patients. After adjustment for age, duration of diabetes, HbA1c, and albumin excretion rate, significant risk factors for moderate-severe nonproliferative retinopathy were blood pressure and triglyceride, and risk factors for proliferative retinopathy were triglyceride and fibrinogen. CONCLUSION: Vision loss is a common complication of patients with insulin-dependent diabetes, with diabetic retinopathy an important cause. Apart from poor glycemic control, several other potentially modifiable risk factors for retinopathy may be important, including elevated blood pressure, plasma triglyceride, and fibrinogen. In view of the possible barriers to the full implementation of strict glycemic control in this type of diabetes, additional strategies for the prevention and slowing of progression of retinopathy should be investigated, such as blood pressure and lipid lowering therapies.

Adolescent↗
PubMed1997

Multicultural health care: reconciling universalism and particularism.

One of the issues of concern in multicultural health care is the degree to which one universal (or mainstream) service can meet the needs of all groups and the extent to which specialist (or ethno-specific) services are required to meet the needs of particular groups. In order to advance debate on this issue, multiculturalism is examined against concepts of identity, equality, bureaucracy and participation. While the appeal of universal healthcare services is that they appear to deliver equal health care to all, they in fact systematically advantage those whose values most closely fit with the dominant social norms. Although ethnic-specific services may overcome this problem, in that they enable 'tailor-made' care, it is unlikely that they would be able to meet all of the health needs of all people from ethnic minorities, especially in locations where numbers are low. Ethnic minority participation in the processes of the health system is proposed as a way for the universal health system to reconcile the need to treat people equally (universalism), but in accordance with their unique and different needs (particularism).

Australia↗
PubMed1997

Naked DNA vaccines expressing the prM and E genes of Russian spring summer encephalitis virus and Central European encephalitis virus protect mice from homologous and heterologous challenge.

Naked DNA vaccines expressing the prM and E genes of two tick-borne flaviviruses, Russian spring summer encephalitis (RSSE) virus and Central European encephalitis (CEE) virus were evaluated in mice. The vaccines were administered by particle bombardment of DNA-coated gold beads by Accell gene gun inoculation. Two immunizations of 0.5 to 1 microg of RSSE or CEE constructs/dose, delivered at 4-week intervals, elicited cross-reactive antibodies detectable by enzyme-linked immunosorbent assay and high-titer neutralizing antibodies to CEE virus. Cross-challenge experiments demonstrated that either vaccine induced protective immunity to homologous or heterologous RSSE or CEE virus challenge. The absence of antibody titer increases after challenge and the presence of antibodies to E and prM, but not NS1, both before and after challenge suggest that the vaccines prevented productive replication of the challenge virus. One vaccination with 0.5 microg of CEE virus DNA provided protective immunity for at least 2 months, and two vaccinations protected mice from challenge with CEE virus for at least 6 months.

Animals↗
PubMed1997

Discriminating between barley genotypes using microsatellite markers.

Eleven microsatellite loci were used to survey 24 barley genotypes representing 23 cultivars and a breeding line in official trials. Three separate combinations of four microsatellites had overall probabilities of identity of less than 1 in 1000 and could distinguish between all 24 barley genotypes. It is shown that the microsatellites could distinguish genotypes with the same pedigree and also that patterns of discrimination were different from those obtained from botanical descriptors. The stability of microsatellites across different generations was demonstrated by a retrospective analysis of the pedigree of Golden Promise. One of the parents of Maythorpe, the immediate ancestor of Golden Promise, was shown to be Irish Goldthorpe rather than Goldthorpe, thereby resolving conflicting published pedigrees.

DNA, Plant↗
PubMed1997

LPS-induced anorexia in leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice.

Administration of endotoxin (lipopolysaccharide, LPS) induces profound anorexia. Injection of leptin decreases food intake in mice. Recently, we reported that LPS and cytokines increase leptin levels in hamsters. To further investigate the role of leptin in the LPS-induced anorexia, we administered LPS to leptin receptor-deficient (db/db) and leptin-deficient (ob/ob) mice. We found that LPS caused anorexia in both db/db and ob/ob mice. As might be predicted if leptin had a role in anorexia, the db/db mice were somewhat resistant to LPS-induced anorexia. However the ob/ob mice were more sensitive to LPS-induced anorexia. No differences between db/db and ob/ob mice and their respective littermate were observed in circulating tumor necrosis factor levels after LPS. These data suggest that leptin per se is not essential for LPS-induced anorexia.

Analysis of Variance↗
PubMed1996

Endotoxin and cytokines decrease serum levels and extra hepatic protein and mRNA levels of cholesteryl ester transfer protein in syrian hamsters.

Endotoxin alters the metabolism of lipoproteins, including that of high density lipoprotein (HDL). Cholesteryl ester transfer protein (CETP) facilitates exchange of HDL cholesterol for very low density lipoprotein (VLDL) triglyceride, leading to catabolism of HDL. We investigated the effects of endotoxin and cytokines on CETP in Syrian hamsters. Endotoxin induced a rapid and progressive decrease in serum CETP levels, by 48 h CETP had decreased to < 20% of control levels. Endotoxin also decreased CETP mRNA and protein levels in adipose tissue, heart, and muscle, the tissues with highest levels of CETP mRNA, providing a plausible mechanism for the endotoxin-induced decrease in circulating CETP. Dexamethasone did not mimic the effects of endotoxin on CETP, but the combination of tumor necrosis factor and interleukin-1 did, indicating that these cytokines may in part mediate the effects of endotoxin on CETP. The endotoxin-induced decrease in CETP may help maintain HDL cholesterol levels during infection and inflammation when increased triglyceride levels could drive the exchange of HDL cholesteryl ester for VLDL triglyceride. Maintaining circulating HDL may be important because HDL protects against the toxic effects of endotoxin and provides cholesterol for peripheral cells involved in the immune response and tissue repair.

Adipose Tissue↗
PubMed1996

Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters.

The expression of leptin, the ob gene product, is increased in adipose tissue in response to feeding and energy repletion, while leptin decreases food intake. Because adipose tissue gene expression is regulated by cytokines induced during infection and because infection is associated with anorexia, we tested whether induction of leptin might occur during the host response to infection. Administration of endotoxin (LPS), a model for gram negative infections, induces profound anorexia and weight loss in hamsters. In fasted adipose tissue to levels similar to fed control animals. There is a strong inverse correlation between mRNA levels of leptin and subsequent food intake. TNF and IL-1, mediators of the host response to LPS, also induced anorexia and increased levels of leptin in mRNA in adipose tissue. As assessed by immuknoprecipitation and Western blotting, circulating leptin protein is regulated by LPS and cytokines in parallel to regulation of adipose tissue leptin mRNA. Induction of leptin during the host response to infection may contribute to the anorexia of infection.

Adipocytes↗
PubMed1996

The radial artery as a bypass graft.

The radial artery is being reintroduced into clinical practice to increase the number of arterial grafts for patients undergoing coronary artery bypass surgery. The radial artery is readily available from one or both forearms and removal is safe in patients who have a normal collateral circulation to the hand. Harvesting the radial artery with the adjacent veins using a minimal touch technique and vasodilators will prevent vasospasm and possibly early occlusion. A concern is that subclinical atheroma is present in many patients. The radial artery can be used as a single graft, anastomosed in a "Y" fashion with the internal mammary artery, or used as a sequential graft. The early mortality and complications are low. There are potential cost savings because the need for an incision in the leg is avoided, so that patients may be discharged early. The early results of radial artery grafting are encouraging. Further follow-up is required to determine the late patency and effects on survival of using the radial artery graft.

Aged↗