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S Jones

Publications and source records attributed to S Jones.

At least 109 records · Page 6Linked to original sources

Protein-RNA interactions: a structural analysis.

A detailed computational analysis of 32 protein-RNA complexes is presented. A number of physical and chemical properties of the intermolecular interfaces are calculated and compared with those observed in protein-double-stranded DNA and protein-single-stranded DNA complexes. The interface properties of the protein-RNA complexes reveal the diverse nature of the binding sites. van der Waals contacts played a more prevalent role than hydrogen bond contacts, and preferential binding to guanine and uracil was observed. The positively charged residue, arginine, and the single aromatic residues, phenylalanine and tyrosine, all played key roles in the RNA binding sites. A comparison between protein-RNA and protein-DNA complexes showed that whilst base and backbone contacts (both hydrogen bonding and van der Waals) were observed with equal frequency in the protein-RNA complexes, backbone contacts were more dominant in the protein-DNA complexes. Although similar modes of secondary structure interactions have been observed in RNA and DNA binding proteins, the current analysis emphasises the differences that exist between the two types of nucleic acid binding protein at the atomic contact level.

Base Pairing↗

Estrogen replacement therapy after breast cancer: a 12-year follow-up.

BACKGROUND: In the United States, estrogen replacement therapy (ERT) is discouraged in breast cancer survivors because of concerns that hormones may reactivate the disease. Because ERT can improve quality of life and decrease morbidity from osteoporosis and cardiovascular disease, however, this policy is increasingly being challenged. METHODS: From February to August 1995, 607 breast cancer survivors were interviewed concerning ERT usage. Sixty-four patients indicated they received some form of ERT after their breast cancer diagnosis. Medical records for these patients were analyzed for disease stage, surgical treatment, adjuvant treatment, estrogen and progesterone receptor status, date of initiation of ERT, type of ERT, recurrence, and final outcome. Patients receiving ERT were followed prospectively. RESULTS: Eight patients were excluded because they had used only vaginal cream ERT. The remaining 56 received ERT as conjugated estrogens, an estradiol patch, estropipate, or birth control pills. The median follow-up from diagnosis was 12.8 years (range, 4.7-38.9 years). The median time on ERT since diagnosis was 6.4 years (range, 1.0-20.9 years); 38% of the patients initiated ERT within 2 years of diagnosis. Estrogen receptors were positive in 28 (74%) of the 38 cases with available information. Pathological disease stage at time of diagnosis and treatment was 0 in 15 cases (27%), I in 27 (48%), and II in 14 (25%). Twenty-six patients (47%) received adjuvant chemotherapy or hormonal therapy. One local recurrence and one contralateral breast cancer occurred during the follow-up period (13.5 and 9.6 years, respectively), with no regional or distant recurrences, for a 15-year actuarial disease-free survival rate of 92.5%. There were no breast cancer deaths. CONCLUSIONS: Use of ERT in a cohort of breast cancer survivors with tumors of generally good prognosis was not associated with increased breast cancer events compared with non-ERT users, even over a long follow-up period.

Adult↗

Functional evaluation of the modified Elmslie-Trillat procedure for patello-femoral dysfunction.

A series of 28 knees in 27 patients were evaluated at an average of 36 months following surgical treatment for patella dislocation, patello-femoral pain, or a combination of both. All cases were treated by the modified Elmslie-Trillat procedure, which involves a lateral retinacular release and medialisation of the tibial tubercle on a distal pedicle. The evaluation included subjective, objective (Fulkerson and Kujala functional knee scores) and radiographic assessments. Subjectively, eight knees (28%) had excellent results, nine knees (33%) good results and seven knees (25%) fair results, accounting for an overall improvement of 86% over the preoperative status. All the knees in patients with a primary symptom of patella dislocation had an excellent or good subjective result, whilst only four knees (40%) in those patients with a primary symptom of pain and four knees (44%) in those with both pain and dislocation had a good or excellent result. The mean objective knee score was excellent for patients with dislocation only, and fair for those with only pain or both pain and dislocation. There have been no further episodes of dislocation in all patients. Six knees (21%) required later screw removal. The modified Elmslie-Trillat procedure produces a favourable outcome in patients with patella dislocation.

Adolescent↗

Il-6 and its soluble receptor orchestrate a temporal switch in the pattern of leukocyte recruitment seen during acute inflammation.

During acute inflammation, leukocyte recruitment is characterized by an initial infiltration of neutrophils, which are later replaced by a more sustained population of mononuclear cells. Based on both clinical and experimental evidence, we present a role for IL-6 and its soluble receptor (sIL-6R) in controlling this pattern of leukocyte recruitment during peritoneal inflammation. Liberation of sIL-6R from the initial neutrophil infiltrate acts as a regulator of CXC and CC chemokine expression, which contributes to a suppression of neutrophil recruitment and the concurrent attraction of mononuclear leukocytes. Soluble IL-6R-mediated signaling is therefore an important intermediary in the resolution of inflammation and supports transition between the early predominantly neutrophilic stage of an infection and the more sustained mononuclear cell influx.

Animals↗

Asthma management and perceptions in rural South Africa.

BACKGROUND: Many First World countries have endeavored to measure the impact of asthma on individuals with asthma and, in addition to this quality of life evaluation, have attempted to define the quality of care for this common chronic illness. OBJECTIVE: The primary objective of this research probe was to assist the National Asthma Program in South Africa with the formulation and delivery of its outreach program to rural asthmatic patients. METHODS: A discussion/questionnaire document was compiled by Partners in Research from established literature. All interviews were conducted in either the clinics, hospitals, or respondents' homes. Both adult asthmatic patients and parents of pediatric asthmatic patients were interviewed. Interviewing took place at seven rural health clinics across South Africa. Each interview included extensive demographic details, questions on asthma definition, symptoms and symptom triggers, family history, age at diagnosis, frequency of symptoms, and treatment. RESULTS: Thirty-five adult asthmatic patients and 27 parents of pediatric asthmatic patients were interviewed. Of the adults, 40% reported wheezing at least once a week (despite diagnosis and treatment) and 19% of children reported similar symptom exacerbations. Fifty-one percent of adults and 56% of children were awakened at least once a week by cough or wheeze. Quality of life measurement reflected that, on average, 37% of responders were frightened during an acute asthma attack, and 68% of parents reported fearing the death of their asthmatic children. Fifty-one percent of adults and 33% of children had been hospitalized at least once for asthma. Although respondents claimed regular training in use of inhaler device, only 43% of adults completed each step correctly. CONCLUSIONS: There is a great deal of fear and ignorance surrounding asthma and, therefore, there is a real need for a greater level of patient education even in the rural areas of South Africa. In rural South Africa, attention should be paid to nurses, because they play a greater role than doctors in management and education of asthma.

Adolescent↗

Features of carnitine palmitoyltransferase type I deficiency.

Carnitine palmitoyltransferase type I (CPT I) is unique among long-chain fatty acid oxidation enzymes in that there are two tissue-specific isoforms, 'hepatic' and 'muscle', which are encoded by two separate genes. The 'hepatic' isoform is expressed in liver, kidney and fibroblasts and at low levels in the heart, while the other isoform occurs in skeletal muscle and is the predominant form in heart. Reported patients with CPT I deficiency lack activity of the hepatic isoform and present before 30 months of age with hypoketotic hypoglycaemia, hepatomegaly with raised transaminases, seizures and coma. We discuss four new cases in three families showing, variously, renal tubular acidosis, transient hyperlipidaemia and, paradoxically, myopathy with elevated creatinine kinase or cardiac involvement in the neonatal period as additional features that deserve wider recognition.

Acidosis, Renal Tubular↗

Identification and characterization of segments 3 and 4 of the ISAV genome.

Infectious Salmon Anaemia is a serious disease of farmed Atlantic Salmon on three continents. The disease causes severe anaemia and haemorrphagic liver necrosis, and carries major economic consequences for affected areas. Nevertheless, the causative agent, a novel orthomyxo-like Virus (Infectious Salmon Anaemia Virus - ISAV), is only partially characterized at the molecular level. We report the isolation and characterization of two novel ISAV segments at the genomic and proteomic levels. These segments are the third and fourth largest of the (ISAV) genome and may code for a nucleocapsid protein (NP) and a polymerase (PA). Western blot analysis using an ISAV polyclonal antibody identified one of these novel proteins as being the major tissue antigen. We discuss the implications of our findings for vaccine development and surveillance of Infectious Salmon Anaemia.

Animals↗

Knowledge about breast cancer risk factors and hereditary breast cancer among early-onset breast cancer survivors.

Little is known about knowledge levels regarding hereditary breast cancer among breast cancer survivors. This study explored, among women with early-onset breast cancer (<50 years): 1) knowledge regarding breast cancer risk factors and hereditary breast cancer; and 2) differences in knowledge based on risk for hereditary disease. Participants recruited from 34 Virginia hospitals responded to two questionnaires. The Family History Questionnaire assessed risk for hereditary breast cancer. The Knowledge, Attitudes, and Beliefs Questionnaire evaluated knowledge of general breast cancer risk factors and hereditary breast cancer. Of 314 respondents, 273 (87%) returned both questionnaires. A total of 137 (52%) participants met the study's criteria for hereditary breast cancer risk. Most participants knew common breast cancer-associated risk factors, including family history of breast cancer. Only 35% recognized family history of non-breast malignancies as a risk factor for breast cancer. Most participants recognized that prophylactic mastectomy does not eliminate breast cancer risk (63%), that not all women carrying a mutation develop disease (73%), and that men can develop breast cancer (96%). The majority selected 'I don't know' for knowledge of several characteristics of hereditary breast cancer, including: early-onset disease (54%); multifocal or bilateral disease (62%); risk transmission through fathers (58%); association with other cancer types (61%); and male breast cancer (70%). Knowledge regarding hereditary breast cancer did not vary between women with suspected hereditary disease and those with presumed sporadic disease. These data highlight the need for information regarding hereditary breast cancer for early-onset breast cancer survivors.

Age of Onset↗

Association analysis of NOTCH4 loci in schizophrenia using family and population-based controls.

A genetic association between NOTCH4 and schizophrenia has previously been proposed. Unsing all markers previously shown to be associated, we found no evidence for such in three independent family-based samples (n=519 parent-offspring trios), and a case-control sample derived from the same ethnic background as the original observation. These data strongly suggest that NOTCH4 is not a significant susceptibility allele for schizophrenia.

Case-Control Studies↗

A spermine-coupled cholesterol metabolite from the shark with potent appetite suppressant and antidiabetic properties.

OBJECTIVE: We describe the pharmacological properties of a novel spermine-cholesterol adduct, MSI 1436 (3beta-N-1(spermine)-7alpha, 24R-dihydroxy-5alpha-cholestane 24-sulfate), which causes reversible suppression of food and fluid intake in mammals resulting in profound weight loss, not associated with other signs or symptoms of illness, and which exhibits antidiabetic properties in genetically obese mice. METHODS: Wild-type rodents and strains with genetic obesity were studied. Effects on food and fluid intake, body weight and composition were examined along with pharmacological and toxicological parameters. RESULTS: MSI-1436 induces profound inhibition of food and fluid intake in rats and mice, resulting in significant weight loss. MSI-1436 is active when introduced directly into the third ventricle of the rat, suggesting the compound acts on central targets. Pair-feeding studies suggest that MSI-1436 causes weight loss by suppressing food intake. Fluid intake is also profoundly reduced but animals remain normally hydrated and defend both water and electrolyte balance from parenteral administration. MSI-1436 is active in ob/ob, db/db, agouti and MC4 receptor knockout mice. MSI-1436 has been administered to ob/ob mice over a 4 month period via a regimen that safely controls body weight, glucose homeostasis and serum cholesterol levels. Following MSI-1436 treatment, db/db mice preferentially mobilize adipose tissue and hyperglycemia is corrected. CONCLUSION: A naturally occurring spermine metabolite of cholesterol, isolated from the dogfish shark, Squalus acanthias, has been identified that induces profound reduction in food and fluid intake in rodents in a setting where thirst is preserved and fluid and electrolyte homeostasis appears to be functioning normally. MSI-1436 probably acts on a central target involving neural circuits that lie downstream from the leptin and the MC4 receptors. Although long-term administration can be accomplished safely in mice, the utility of this compound as a potential human therapeutic awaits an analysis of its pharmacological properties in man.

Animals↗

Evaluating primary care as a base for medical education: the report of the Cambridge Community-based Clinical Course.

BACKGROUND: Medical students receive increasing amounts of their clinical education in a primary care setting. The educational possibilities of such attachments are still being explored. AIM: To report the evaluation of a small, radical innovation to provide students with a long-term community attachment which integrated with hospital-based education. METHOD: Between 1993 and 1998, 13 medical students completed 15-month attachments with a single general practice in England. The course offered them experience in the major clinical specialties throughout this period. Students were exposed to specialist as well as generalist education in the context of patients with whom they could establish a continuing relationship. The innovation was evaluated by its feasibility, by students' examination results, by analysis of clinical experience, through formal student feedback and by cost. RESULTS: The course was practicable in a particular setting with academic leadership. The students all passed their exams. They had wide, appropriate clinical experience even though the attachment was to a single practice. When they returned to the hospital environment, students did not feel themselves at a disadvantage compared with traditional students. The costs of the course are controversial: placement costs were higher than in the hospital, but those for facilities were lower. CONCLUSION: It is possible to run a course like this successfully. It remains the most radical attempt to share clinical education in the UK between primary and secondary/tertiary care. Further research is required into providing long-term clinical attachments in NHS primary care settings.

Clinical Competence↗

Bicarbonate/lactate-based peritoneal dialysis solution increases cancer antigen 125 and decreases hyaluronic acid levels.

BACKGROUND: In a randomized, controlled trial comparing a pH neutral, bicarbonate/lactate (B/L)-buffered PD solution to conventional acidic, lactate-buffered solution (C), the overnight dialysate levels of markers of inflammation/wound healing [hyaluronic acid (HA)], mesothelial cell mass/membrane integrity [cancer antigen 125 (CA125)], and fibrosis [transforming growth factor-beta1 (TGF-beta1) and procollagen I peptides (PICP)] were assessed over a six-month treatment period. METHODS: One hundred six patients were randomized (2:1) to either the B/L group or C group. Overnight effluents were collected at entry into the study (time = 0 all patients on control solution) and then at three and six months after randomization. Aliquots were filtered, stored frozen, and assayed for HA, CA125, TGF-beta1, and PICP. Differences between groups were assessed by repeated-measures analysis of variance for unbalanced data using the SAS procedure MIXED. RESULTS: In patients treated with B/L, there was a significant (P = 0.03) increase in CA125 after six months compared with time = 0 (19.76 +/- 11.8 vs. 24.4 +/- 13.8 U/mL; mean +/- SD; N = 51). In the same group of patients, HA levels were significantly decreased at both three and six months in the B/L-treated group (time = 0, 336.0 +/- 195.2; time = 3 months, 250.6 +/- 167.6; and time = 6 months, 290.5 +/- 224.6 ng/mL; mean +/- SD; P = 0.006, N = 47 and P = 0.003, N = 48, respectively). No significant changes in CA125 or HA levels were observed in the control group. There were no significant changes observed in the levels of PICP or TGF-beta1 in the B/L or C group over the six-month treatment period. CONCLUSIONS: These results suggest that continuous therapy with the B/L solutions modulates the levels of putative markers of peritoneal membrane integrity and inflammation. In the long term, this may positively impact the peritoneal membrane, increasing its life as a dialyzing organ.

Adult↗

Regulation of renal proximal tubular epithelial cell hyaluronan generation: implications for diabetic nephropathy.

BACKGROUND: Proximal tubular cells (PTCs) contribute to pathological changes in the renal interstitium by the generation of cytokines and alterations in the composition of the extracellular matrix. Hyaluronan (HA) is a ubiquitous connective tissue polysaccharide that regulates cell function and tissue remodeling. In the current study, we investigated the regulation of HA generation by PTCs. METHODS: Primary cultures of human PTCs were grown to confluence and stimulated under serum-free conditions with either interleukin-1 (IL-1) or 25 mmol/L D-glucose. Alterations in HA generation were detected by enzyme-linked immunosorbent assay, and alterations in HA synthase gene expression were examined by reverse transcription-polymerase chain reaction. Subsequently, the mechanisms of IL-1 beta and glucose-induced alterations in HA were examined utilizing HK-2 cells. RESULTS: Stimulation of human PTCs (HPTCs) with either IL-1 beta or 25 mmol/L D-glucose led to a significant increase in the HA concentration in the culture supernatant. In contrast, stimulation of HPTCs with transforming growth factor-beta1, basic fibroblast growth factor, or platelet-derived growth factor-AB did not stimulate HA production. The addition of IL-1 beta or 25 mmol/L D-glucose also increased HA generation in HK-2 cells and was associated with the induction of HAS2 mRNA. HAS3 mRNA was constitutively expressed and was not influenced by the addition of either stimulus. HAS1 mRNA expression was not detected in either unstimulated or stimulated cells. Inhibition of gene transcription or protein synthesis abolished HA production in response to either IL-1 beta or glucose. Inhibition of nuclear factor-kappa B (NF-kappa B) activation either by sulindac or by the proteosome inhibitor (PSI) abrogated both IL-1 beta and glucose-mediated alteration in HA synthesis. CONCLUSION: This study demonstrates, to our knowledge for the first time, that increased HA synthesis in response to either IL-1 beta or elevated 25 mmol/L D-glucose is associated with NF-kappa B-activated transcription of HAS2.

Base Sequence↗

Self-reports and clinician-measured physical function among patients with low back pain: a comparison.

OBJECTIVE: To determine the relationships among self-reported activity limitation and clinician-measured functional performance tests. DESIGN: Case series survey. SETTING: A referral-based orthopedic spine clinic in Houston, TX. PATIENTS: Eighty-three patients (48 women, 35 men) with low back pain (LBP). INTERVENTIONS: The Roland-Morris Disability Questionnaire (RMDQ) and a physical performance test (PPT) battery. MAIN OUTCOME MEASURES: Self-reported activity limitation (eg, walking, bending, getting out of chair, putting on sock, doing heavy jobs) was assessed by the RMDQ. Clinician-measured functional performance was assessed with the PPT, a battery comprised 6 tests: lumbar flexion range of motion, a 50-foot walk at fastest speed, a 5-minute walk, 5 repetitions of sit-to-stand, 10 repetitions of trunk flexion, and loaded reach task (patients reached forward while holding a weight weighing 5% of their body weight). RESULTS: Pearson's product-moment correlations between total RMDQ score and each of the performance tests ranged from.29 to.41. Point biserial correlations between individual RMDQ items and their corresponding performance tests were slightly lower, ranging from.20 to.33. CONCLUSION: There were moderate correlations between self-reported activity limitation and corresponding clinician-measured performance tests. The unique perspective each method provides appears to be useful for a comprehensive understanding of physical function in patients with LBP.

Activities of Daily Living↗

It is past due.

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Government↗

The interleukin 1 receptor antagonist gene allele 2 as a predictor of pouchitis following colectomy and IPAA in ulcerative colitis.

BACKGROUND & AIMS: The interleukin 1 receptor antagonist gene allele 2 has been suggested as a determinant of both disease susceptibility and extent in ulcerative colitis. The aim of this study was to assess the allele as a predictor of both the indication for colectomy and the occurrence of pouchitis after ileal pouch-anal anastomosis formation. METHODS: Genotyping for the +2018 single nucleotide polymorphism in the interleukin 1 receptor antagonist gene was performed in 109 patients who had undergone colectomy, including 82 patients who had been followed prospectively after ileal pouch-anal anastomosis formation. RESULTS: Patients with pouchitis had a higher allele 2 carriage rate compared with those without pouchitis (72% vs. 45%) and Kaplan-Meier survival analysis showed that allele 2 carriers had a significantly increased incidence of pouchitis compared with noncarriers (log-rank test, 6.5). After adjustment for confounding covariates in a Cox proportional hazards model, the relative hazard was 3.1 (95% confidence interval [CI], 1.2-7.8; P = 0.02). Although there was a higher allele 2 carriage rate in patients with chronic refractory compared with acute severe ulcerative colitis (63% vs. 48%), this difference was not significant (odds ratio, 1.9; 95% CI, 0.9-4.1; P = 0.1). CONCLUSIONS: The interleukin 1 receptor antagonist gene allele 2 predicts pouchitis after ileal pouch-anal anastomosis in ulcerative colitis.

Adolescent↗