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J Rhodes

Publications and source records attributed to J Rhodes.

At least 91 records · Page 5Linked to original sources
PubMed1995

Galactose oxidation as a potent vaccine adjuvant strategy. Efficacy in murine models and in protection against a bovine parasitic infection.

Potent immunological adjuvants are urgently required to complement subunit protein and peptide vaccines in prophylactic and therapeutic vaccination. Carbonyl-amino condensations, which are essential to the inductive interaction between antigen-presenting cells and T-helper cells, were tested as a target for the enhancement or immune responses to vaccine antigens. Enzymic oxidation of cell surface galactose by the novel adjuvant NAGO, to increase amine-reactive carbonyl groups on lymphocytes and antigen-presenting cells, provided a potent noninflammatory method of enhancing the immunogenicity of viral, bacterial, and protozoal subunit vaccines in mice. In pilot protection studies with a glutathione-S-transferase vaccine against bovine Fasciola hepatica, a formulation containing NAGO as sole adjuvant agent proved very effective in inducing protection. In terms of protection in individual animals, NAGO alone was better than Quil A emulsified in squalene Montanide (five of eight animals were protected better than 80% by NAGO; four of eight animals were protected better than 93% by NAGO; two of eight animals were protected better than 80% by QA/SM). QA/SM (69% mean protection) was, however, more consistent overall than NAGO (65% mean protection). NAGO proved more effective in murine models when combined with muramyl dipeptide, but this combination has yet to be tested in protection studies.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1995

Transdermal nicotine as maintenance therapy for ulcerative colitis.

BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers. Having found previously that treatment with transdermal nicotine patches and mesalamine (5-aminosalicylic acid) has a beneficial effect on active colitis, we examined the value of transdermal nicotine for the maintenance of remission. METHODS: We treated 80 patients with ulcerative colitis in remission with either transdermal nicotine or placebo patches for six months in a randomized, double-blind study. Incremental doses of nicotine were given for the first three weeks to achieve a maintenance dose; most patients tolerated 15 mg for 16 hours daily. All patients were taking mesalamine preparations as maintenance treatment at entry into the study; this treatment was stopped once the maintenance dose of nicotine was achieved. Clinical, sigmoidoscopic, and histologic assessments were made at the beginning and the end of the study, or at relapse. Side effects and serum nicotine and cotinine concentrations were monitored throughout the study. RESULTS: There was no significant difference in the number of relapses between the groups. Twenty-two patients in the nicotine group were prematurely withdrawn from the study, 14 because of relapse and 8 for other reasons, including side effects and protocol violations. In the placebo group, 20 patients were withdrawn prematurely, 17 because of relapse and 3 for other reasons. Among patients using 15-mg nicotine patches, serum nicotine and cotinine concentrations were lower than expected and may reflect poor compliance. Side effects were reported by 35 patients--21 in the nicotine group and 14 in the placebo group--the most common of which were nausea, lightheadedness, and itching. CONCLUSIONS: Transdermal nicotine alone was no better than placebo in the maintenance of remission of ulcerative colitis, and premature withdrawal due to side effects was more common in the nicotine group.

Administration, Cutaneous↗
PubMed1995

Alteration of DNA and RNA binding activity of human telomere binding proteins occurs during cellular senescence.

The loss of telomere sequences during in vitro and in vivo aging suggests that mechanisms affecting telomere length may have important consequences in cellular senescence. In this study, we have found that the activity of single-stranded telomere binding proteins is increased in nuclear extracts prepared from senescent human diploid fibroblasts compared to actively growing cells. Since single-stranded telomere binding proteins are closely related to RNA binding proteins, we examined the binding activity of several major RNA binding proteins to RNA by uv cross-linking. The level of activity was greatly diminished and the overall pattern of uv cross-linked products were altered in extracts prepared from senescent cells. Furthermore, Western analysis revealed a concurrent decrease in senescent extracts of the protein level for many RNA binding proteins, including those which bind to telomere sequence. Although the reduction in the level of these proteins parallels the reduced activity in RNA binding, the paradoxical increased telomere binding activity exhibited by extracts from older cells suggests a complex relationship between these proteins with RNA and DNA. Moreover, the reduced RNA binding activity of these proteins indicates that the biochemical function of several RNA binding proteins is compromised during cellular senescence, raising an intriguing possibility that a change in pre-mRNA metabolism may contribute to the multitude of changes in gene expression observed in cellular senescence.

Base Sequence↗
PubMed1995

Incidence of Crohn's disease in Cardiff over 60 years: 1986-1990 an update.

OBJECTIVE: To report the incidence of Crohn's disease in the city of Cardiff between 1986 and 1990 and relate it to our previous incidence figures which extend over 60 years. METHODS: The incidence of Crohn's disease was examined using hospital diagnostic indices supplemented by records from clinicians and from the Department of Pathology, University Hospital of Wales, Cardiff, UK. In addition, a questionnaire was sent to all family practitioners in Cardiff asking them to identify patients in their practice. RESULTS: Eighty-six new patients were confirmed after reviewing the notes of patients in whom a diagnosis of Crohn's disease was considered. The mean incidence for this quinquennium was 5.9 cases per 10(5) of the population per year (95% confidence interval 4.7-7.3), with the highest age-specific incidence between those aged 15 and 34 years. Colorectal disease was the most common site of disease at the time of diagnosis and this was particularly striking in those aged over 50 years. CONCLUSIONS: The findings are related to our previous studies. The incidence of Crohn's disease has not continued to increase at the rate reported in early 1980s, but remains one of the highest reported in the literature. The colon has become the most commonly affected site, which may reflect an increase in diagnostic awareness.

Adolescent↗
PubMed1995

A homeodomain protein selectively expressed in noradrenergic tissue regulates transcription of neurotransmitter biosynthetic genes.

In order to characterize the specificity of expression of the neurotransmitter biosynthetic gene dopamine beta-hydroxylase (DBH), the identification of proteins that interact with the DB1 enhancer was initiated. A homeobox-containing cDNA was isolated from a PC12 expression cDNA library screened with the DB1 enhancer. The homeodomain is a member of the paired-like class, and is encoded by several nonidentical cDNAs. The cDNAs contain the same sequence in the homeodomain and 3' coding and noncoding sequences, but diverge in sequence 5' to the homeodomain. This family of homeobox-containing cDNAs is named Arix. Arix mRNA transcripts are found only in noradrenergic, DBH-positive tissues, and in cell lines derived from those tissue. The DB1 enhancer contains two binding sites for the Arix homeodomain, and both sites contribute to basal activity of the DBH promoter. When introduced into tissue culture, Arix regulates the transcriptional activity from the DBH promoter, and also from the promoter of the tyrosine hydroxylase gene, encoding the initial enzyme of the catecholamine biosynthetic pathway. The pattern of expression of the Arix transcripts, the presence of the homeodomain, and the transcriptional regulatory properties suggest that this family of proteins may be involved in the specificity of expression of the catecholamine biosynthetic genes.

Amino Acid Sequence↗
PubMed1994

Transdermal nicotine for active ulcerative colitis.

BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers. Because anecdotal reports suggest that smoking and nicotine may improve the symptoms of the disease, we examined the effect of nicotine as a supplemental treatment for ulcerative colitis. METHODS: We treated 72 patients with active ulcerative colitis with either transdermal nicotine patches or placebo patches for six weeks in a randomized, double-blind study. Incremental doses of nicotine were given; most patients tolerated doses of 15 to 25 mg per 24 hours. All the patients had been taking mesalamine, and 12 were receiving low doses of glucocorticoids; these medications were continued without change during the study. Clinical, sigmoidoscopic, and histologic assessments were made at base line and at the end of the study; symptoms were recorded daily on a diary card, and the clinician made a global assessment. Side effects and plasma nicotine and cotinine concentrations were monitored throughout the study. RESULTS: Seventeen of the 35 patients in the nicotine group had complete remissions, as compared with 9 of the 37 patients in the placebo group (P = 0.03). The patients in the nicotine group had greater improvement in the global clinical grade of colitis (P < 0.001) and the histologic grade (P = 0.03), lower stool frequency (a difference of 1.6 stools daily; P = 0.008), less abdominal pain (P = 0.05), and less fecal urgency (P = 0.009). More patients in the nicotine group had side effects (23, vs. 11 in the placebo group; P = 0.002), the most common of which were nausea, lightheadedness, headache, and sleep disturbance. Withdrawals due to ineffective therapy were more common in the placebo group (3 vs. 8, P = 0.12). CONCLUSIONS: The addition of transdermal nicotine to conventional maintenance therapy improves symptoms in patients with ulcerative colitis.

Administration, Cutaneous↗
PubMed1994

Teaching social and behavioural sciences: have we delivered--have they got it?

The inception of Project 2000 and its new curriculum has set a requirement for the teaching of Social and Behavioural Sciences in the nursing programme. Subjects covered are Health Promotion, Sociology/Social Policy, Psychology, Research and Computers. These subjects are complex and this paper outlines the problems and difficulties experienced by teachers since the start of the course in 1991. The problems experienced by the students in relating theory to practice are also discussed.

Behavioral Sciences↗
PubMed1994

Physiologic significance of chronic coronary aneurysms in patients with Kawasaki disease.

OBJECTIVES: The aim of this study was to determine whether persistent coronary aneurysms in patients with Kawasaki disease are associated with altered myocardial perfusion and function. BACKGROUND: Some patients with Kawasaki disease have died suddenly because of severe coronary artery stenosis; others have chronic coronary aneurysms. METHODS: Eleven patients with chronic coronary aneurysms were enrolled in the study. The size of the aneurysms and the degree of associated stenosis were determined by angiography in nine patients and by echocardiography in two. All patients underwent simultaneous function and myocardial perfusion assessment during symptom-limited exercise by echocardiography and technetium-99m sestamibi imaging, respectively. RESULTS: Of 33 vascular territories, 18 contained coronary aneurysms measuring 3.5 to 10 mm. Three aneurysms were associated with significant stenosis as detected by angiography. Of the 18 vascular territories, 13 were normal, and 5 manifested stress-induced perfusion defects; of the latter 5 areas, 4 had associated wall motion abnormalities. The three territories supplied by stenotic coronary arteries had both abnormal regional function and perfusion demonstrated during exercise. CONCLUSIONS: Patients with chronic coronary aneurysms may have associated stenosis, as detected by angiography, with a subjacent myocardium that is subject to abnormal perfusion and function. However, the majority of coronary aneurysms are associated with normal regional coronary flow reserve, as assessed by myocardial perfusion imaging, and even giant coronary aneurysms may be associated with normal coronary flow reserve and preserved regional myocardial function during stress.

Adolescent↗
PubMed1994

Prevention of rebleeding from oesophageal varices: two-year follow up of a prospective controlled trial of propranolol in addition to sclerotherapy.

A prospective randomised trial comparing propranolol and sclerotherapy to sclerotherapy alone was conducted over a 2-year follow up in a district hospital setting of unselected patients. Rebleeding and survival were analysed. Thirty-nine patients were randomised to propranolol plus sclerotherapy and 34 to sclerotherapy alone. The two groups were clinically comparable. There was no significant difference in the cumulative percent of patients free of rebleeding; 54% of the sclerotherapy group rebled compared to 52% of the group treated with propranolol plus sclerotherapy (Hazard ratio 1.09 (0.54-2.22) and p = 0.81, NS). Two-year actuarial survival was also not significantly different, with 77% of the propanolol plus sclerotherapy group surviving, compared to 74% of sclerotherapy alone (Hazard ratio 1.08 (0.35-2.22) and p = 0.79, NS). The mean time to eradication of varices was not significantly different between the two groups (propranolol plus sclerotherapy 222 days, sclerotherapy alone 243 days), nor did the rate of variceal recurrence differ (72.7 vs 72 days). This study did not show long-term improvement in rebleeding or survival using propranolol in addition to a regular sclerotherapy programme.

Adolescent↗
PubMed1994

Cigarette smoking is not a risk factor in atopic dermatitis.

BACKGROUND: In recent years several diseases have been shown to have a relationship with smoking. Psoriasis is largely a disease of smokers, whereas acne appears to be associated with not smoking. METHODS: One hundred and fifty patients with atopic dermatitis were sent a postal questionnaire on smoking habits and the results were compared with those from matched controls in the local community. RESULTS: One hundred and twenty-seven patients (85%) completed the questionnaire. There was no apparent difference in the prevalence of current smokers amongst atopic dermatitis patients compared with controls (odds ratio = 1.1, 95% confidence limits 0.65-1.86, P = 0.8). CONCLUSIONS: There was no significant difference between the smoking prevalence of patients with atopic dermatitis and matched controls.

Dermatitis, Atopic↗
PubMed1994

Thickness of adherent mucus gel on colonic mucosa in humans and its relevance to colitis.

The thickness of adherent mucus gel on the surface of colonic mucosa was measured in surgically resected specimens from 46 'control' patients most of whom had carcinoma of the colon; 12 were from right colon, 17 left colon, and 21 from rectum. In addition specimens were examined from 17 patients with ulcerative colitis and 15 patients with Crohn's disease. In controls a continuous layer of mucus was readily seen on specially prepared sections viewed by phase contrast illumination. Mean values for right and left colon and rectum were 107 (48), 134 (68), and 155 (54) microns respectively with a significant difference between right colon and rectum (p = 0.015). Values in ulcerative colitis showed greater variation and in those areas with acute inflammation mucosa was denuded of the mucus layer. In contrast, values for Crohn's disease were normal or greater than normal in thickness--right colon 190 (83) microns compared with 107 48 microns, p = 0.0093. A series of validation experiments are described for the method used to measure mucus thickness. The possible role of mucus in the pathogenesis of inflammatory bowel disease is discussed.

Adolescent↗
PubMed1994

Controlled trial of anti-tuberculous chemotherapy for two years in Crohn's disease.

One hundred and thirty patients with active symptoms of Crohn's disease were treated in a double blind randomised controlled trial with rifampicin, isoniazid, and ethambutol, or identical placebos for up to two years. All other treatment considered necessary was continued. Analyses were based on 126 patients, 63 in each treatment group. Thirty seven in the active and 30 in the placebo group had previous surgical procedures. There was no difference in concomitant treatment between the two groups. Thirty in the active and 46 in the placebo groups were taking corticosteroids at entry to the trial. Forty eight of 63 patients in the active and 49 of 63 in the placebo group, completed at least 12 months' therapy. Reasons for early withdrawal included pregnancy, adverse reaction, and failure to comply. There was no significant difference in the mean number of months completed between the two groups. Nineteen adverse reactions were recorded for 17 patients in the active group compared with three reactions in patients on placebo. All of the nine patients withdrawn early because of adverse reactions were in the active group. Fifteen patients on active treatment and 14 on placebo had surgery during the trial with no difference in the type of surgery required between the groups. Radiological assessments based on 98 patients at the end of the trial showed no significant differences between groups in changes of extent of disease. More patients developed strictures on placebo compared with active treatment but without a statistically significant difference. No differences were found between groups for the total prednisolone dose or the number of days on which prednisolone dose was 10 mg or above. Serial measurements of body weight and Crohn's disease activity index (CDAI) together with blood values for albumin, haemoglobin, white cell count, and platelets showed no consistent different differences between groups. There were occasional significant differences for some of these values between groups, which were not sustained. The trail provides little evidence of tangible benefit from the trail treatment.

Adolescent↗
PubMed1993

Comparison of antigen presentation of influenza A nucleoprotein expressed in attenuated AroA- Salmonella typhimurium with that of live virus.

Rationally attenuated strains of Salmonella expressing foreign proteins represent a potentially important vaccine delivery system. The characteristics of Ag presentation of influenza nucleoprotein expressed in an AroA- strain of Salmonella typhimurium (SL3262-pNP-2) have therefore been compared with those of soluble purified nucleoprotein (NP) and infectious influenza virus. This represents three distinct modes of internalization of the same protein into APC. Human monocytes and the monocytic leukemia cell line THP-1 infected with SL3261-pNP-2 were found to present several different epitopes from NP to human CD4+ class II-restricted T lymphocytes. Ag presentation to these T cell clones was enhanced by pretreatment of THP-1 cells with IFN-gamma but not TNF-alpha. Bacterial phagocytosis and Ag presentation of NP were increased after opsonization of Salmonella with immune serum. Macrophages infected with SL3261-pNP-2 were unable to present NP to class I-restricted T cells. In contrast, cells infected with live influenza virus, although recognized by NP-specific class I-restricted CTL, were inefficiently recognized by NP-specific class II-restricted T cells. Ag presentation to CD4+ T cell clones by monocytes of SL3261-pNP-2, purified recombinant NP, and live influenza virus, but not the synthetic peptide 206-229, was inhibited by chloroquine and the protease inhibitors pepstatin A and leupeptin, suggesting that the major route of processing in each case was via the exogenous pathway. T cell recognition of NP via all of these Ag delivery systems was also abrogated by cycloheximide and brefeldin A treatment, indicating a requirement for recently synthesized MHC class II molecules in presentation of whole NP after processing but not for the corresponding synthetic peptide.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗
PubMed1993

Smoking and ulcerative colitis: a community study.

Smoking habits of patients with ulcerative colitis, diagnosed in the City of Cardiff between the 1st of January 1978 and the 31st of December 1987 were examined. There was a significant deficit of current smokers, an excess of life-long non-smokers and ex-smokers compared with the general population. Men who had previously smoked presented with colitis later than life long non-smokers (mean age difference 16.1 years). The proportion of ex-smokers in this group of patients with colitis was more than twice that expected in the general population. The interval between cessation of smoking and subsequent onset of colitis in ex-smokers was relatively short and in more than half of them occurred within 8 years. There was no significant difference in the frequency of colectomy or the extent of disease among smokers, ex-smokers or life-long non-smokers with ulcerative colitis.

Adult↗
PubMed1993

A four-year longitudinal study of bone loss in patients with inflammatory bowel disease.

Serial measurements of spinal trabecular and radial cortical bone density were made over 4 years in 70 patients with inflammatory bowel disease. Mean rates of bone loss for the cohort differed little from rates reported in normal populations; however, some patients showed increased rates of loss, including patients whose bone density at entry to the study was already well below normal. There was a significant correlation between the amount of corticosteroid prescribed and spinal trabecular bone loss in males, but no significant correlation with other clinical parameters. Increased rates of bone loss emphasise the need for bone densitometry and prophylactic measures in patients with inflammatory bowel disease.

Adult↗