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Biomedical subjects

S Jones

Publications and source records attributed to S Jones.

At least 55 records · Page 3Linked to original sources

Functional correlates of the interleukin-1 receptor antagonist gene polymorphism in the colonic mucosa in ulcerative colitis.

Association studies have identified the interleukin-1 receptor antagonist gene allele 2(IL-1RN*2) as a marker of susceptibility in ulcerative colitis (UC). This study investigated the significance of the IL-1RN genotype with respect to protein and mRNA expression in the colonic mucosa. Homogenates of rectal biopsies from 99 UC and 54 controls were assayed for cytokines IL-1ra, IL-1a and IL-1b using ELISA. IL1RN, IL1A and IL1B genotypes were determined using restriction-enzyme analysis. The ability of the two IL1RN alleles to generate steady-state mRNA accumulation was assessed in the colonic mucosa of seven heterozygous patients. Stepwise linear regression demonstrated that IL-1RN genotype (P=0.001), diagnosis (P<0.0001) and treatment (P<0.03) were independent factors associated with the IL-1ra protein level whilst IL1RN genotype (P=0.005) and macroscopic inflammatory grade (P<0.0001) were associated with the IL-1ra/ total IL-1 ratio. The IL1RN*2 correlated with reduced IL-1ra and IL-1ra/IL-1 ratio with a gene dosage effect. In heterozygous UC patients the ratio of allele 1 mRNA / allele 2 steady state mRNA was always greater than 1 (range: 1.2-3.1) (P=0.018). The IL-1RN*2 is associated with reduced levels of IL-1ra protein and IL-1RN mRNA in the colonic mucosa, providing a biologically plausible explanation for the observed association of the allele with the disease.

3' Untranslated Regions↗

A novel approach to a patient with Crohn disease and a high stoma output: a missed opportunity?

The development of stricturing or penetrating behaviour in Crohn disease is influenced by disease location, clinical activity of the disease and smoking habit. The management of inflammatory bowel disease remains unsatisfactory, and the influence of current therapies--immunosuppressants, and especially the novel biological treatment now commonly used in Crohn disease--remains largely unknown. A relatively smaller number of patients receive dietary treatment as well. Physicians' scepticism, under-resourced dietetic departments and patient compliance are the main concerns in considering enteral nutrition. The management of high stomal output in Crohn disease is even more challenging. We report a case of active Crohn disease with high stoma output treated successfully solely with enteral feeding without the need for surgical intervention or administration of potent pharmacotherapy.

Adult↗

Chlamydia pneumoniae in HIV-infected patients and controls assessed by a novel whole blood interferon-gamma assay, serology and PCR.

Chlamydia pneumoniae seropositivity is associated with cardiovascular disease and HIV infection. Cell-mediated immune responses are important for control of C. pneumoniae, and such responses may be impaired in HIV-infected patients. An assay for detection of interferon (IFN)-gamma in whole blood stimulated with C. pneumoniae antigen was developed and studied in HIV-infected patients and uninfected controls. Among 34 HIV-infected patients, none had an IFN-gamma response to C. pneumoniae antigen, compared with five of 32 healthy controls (p < 0.001). Fewer HIV-infected individuals elicited a serum IgG response when tested with a commercial enzyme immunoassay (p 0.009), but this was not so for serum IgA (p 0.12). Additionally, the IFN-gamma and antibody assays showed a trend towards a bivariate response in normal controls. This indicates that cellular and antibody responses against C. pneumoniae may be mutually exclusive, with potential implications for the role of this organism in the genesis of cardiovascular disease in both immunocompetent and HIV-infected populations.

Adult↗

Multiple cognitive deficits during the transition to Alzheimer's disease.

The literature on cognitive markers in preclinical AD is reviewed. The findings demonstrate that impairment in multiple cognitive domains is typically observed several years before clinical diagnosis. Measures of executive functioning, episodic memory and perceptual speed appear to be most effective at identifying at-risk individuals. The fact that these cognitive domains are most implicated in normal cognitive aging suggests that the cognitive deficit observed preclinically is not qualitatively different from that observed in normal aging. The degree of cognitive impairment prior to the diagnosis of Alzheimer's disease (AD) appears to generalize relatively well across major study characteristics, including sample ascertainment procedures, age and cognitive status of participants, as well as time to diagnosis of dementia. In episodic memory, there is evidence that the size of the preclinical deficit increases with increasing cognitive demands. The global cognitive impairment observed is highly consistent with observations that multiple brain structures and functions are affected long before the diagnosis of AD. However, there is substantial overlap in the distribution of cognitive scores between those who will and those who will not be diagnosed with AD, hence limiting the clinical utility of cognitive markers for early identification of cases. Future research should consider combining cognitive indicators with other types of markers (i.e. social, somatic, genetic, brain-based) in order to increase prediction accuracy.

Aged↗

Scarf osteotomy for hallux valgus. A prospective clinical and pedobarographic study.

We prospectively reviewed 24 patients (35 feet) who had been treated by a Scarf osteotomy and Akin closing-wedge osteotomy for hallux valgus between June 2000 and June 2002. There were three men and 21 women with a mean age of 46 years at the time of surgery. The mean follow-up time was 20 months. Our results showed that 50% of the patients were very satisfied, 42% were satisfied, and 8% were not satisfied. The mean American Orthopaedic Foot and Ankle Society score improved significantly from 52 points pre-operatively to 89 at follow-up (p < 0.001). The intermetatarsal and hallux valgus angles improved from the mean pre-operative values of 15 degrees and 33 degrees to 9 degrees and 14 degrees, respectively. These improvements were significant (p < 0.0001). The change in the distal metatarsal articular angle was not significant (p = 0.18). There was no significant change in the mean pedobarographic measurements of the first and second metatarsals after surgery (p = 0.2). The mean pedobarographic measurements of the first and second metatarsals at more than one year after surgery were within the normal range. Two patients had wound infections which settled after the administration of antibiotics. One patient had an intra-operative fracture of the first metatarsal and one required further surgery to remove a long distal screw which was irritating the medial sesamoids. We conclude that the Scarf osteotomy combined with the Akin closing-wedge osteotomy is safe and effective for the treatment of hallux valgus.

Female↗

Probing scattering wave functions close to the nucleus.

Recently, three-dimensional imaging of the ejected electrons following 100 MeV/amu C6+ single ionization of helium led to the observation of a new structure not predicted by theory [Nature (London) 422, 48 (2003)]]. Instead of the usual "recoil lobe" centered on the momentum-transfer axis, a ring-shaped structure centered on the beam axis was observed. New measurements at 2 MeV/amu exhibit a similar structure, which is now predicted by theory. We argue that the same theory failed at 100 MeV/amu because the faster projectiles probe distances much closer to the nucleus, where our multiple-scattering model is expected to break down.

Journal Article↗

A functional genomic analysis of cell morphology using RNA interference.

BACKGROUND: The diversity of metazoan cell shapes is influenced by the dynamic cytoskeletal network. With the advent of RNA-interference (RNAi) technology, it is now possible to screen systematically for genes controlling specific cell-biological processes, including those required to generate distinct morphologies. RESULTS: We adapted existing RNAi technology in Drosophila cell culture for use in high-throughput screens to enable a comprehensive genetic dissection of cell morphogenesis. To identify genes responsible for the characteristic shape of two morphologically distinct cell lines, we performed RNAi screens in each line with a set of double-stranded RNAs (dsRNAs) targeting 994 predicted cell shape regulators. Using automated fluorescence microscopy to visualize actin filaments, microtubules and DNA, we detected morphological phenotypes for 160 genes, one-third of which have not been previously characterized in vivo. Genes with similar phenotypes corresponded to known components of pathways controlling cytoskeletal organization and cell shape, leading us to propose similar functions for previously uncharacterized genes. Furthermore, we were able to uncover genes acting within a specific pathway using a co-RNAi screen to identify dsRNA suppressors of a cell shape change induced by Pten dsRNA. CONCLUSIONS: Using RNAi, we identified genes that influence cytoskeletal organization and morphology in two distinct cell types. Some genes exhibited similar RNAi phenotypes in both cell types, while others appeared to have cell-type-specific functions, in part reflecting the different mechanisms used to generate a round or a flat cell morphology.

Animals↗

Role of the ground state in electron-atom double ionization.

Recently, absolute measurements have been reported for double ionization of helium by 5.6 keV electron-impact. At this high energy, one would think that the first Born approximation for the interaction of the projectile with the atom would be valid. However, on the basis of a lowest-order implementation of a Faddeev-type approach, Berakdar [Phys. Rev. Lett. 85, 4036 (2000)]] concluded that the approximation was not valid. Here we argue that (i) it is valid at this energy and (ii) the previous discrepancy between calculations in the first Born approximation and the overall magnitude of the measurements was due to a poor description of the ground state.

Journal Article↗

Mutation screening of the Homer gene family and association analysis in schizophrenia.

Homer proteins are a group of proteins that regulate group 1 metabotropic glutamate receptor function. As altered glutamate function has been implicated in many neuro psychiatric disorders, particularly schizophrenia, we have screened all three known Homer genes for sequence variation for use under the candidate gene association paradigm. We found seven SNPs, including three in exons. Of these, none was non-synonymous. Allele frequencies of all the detected SNPs were estimated in DNA pools of 368 schizophrenics and 368 controls. Only one (Homer 1 IVS4 + 18A > G) was associated with schizophrenia in this sample, a finding confirmed by individual genotyping (P = 0.01). However, in our extended sample of 680 cases and 671 controls, the evidence for association diminished (P = 0.05). Our results suggest it is unlikely that sequence variants in the Homer genes contribute to the aetiology of schizophrenia, but the variants we identified are plausible candidates for other neuropsychiatric phenotypes.

Adult↗

Three-dimensional imaging of atomic four-body processes.

To understand the physical processes that occur in nature we need to obtain a solid concept about the 'fundamental' forces acting between pairs of elementary particles. It is also necessary to describe the temporal and spatial evolution of many mutually interacting particles under the influence of these forces. This latter step, known as the few-body problem, remains an important unsolved problem in physics. Experiments involving atomic collisions represent a useful testing ground for studying the few-body problem. For the single ionization of a helium atom by charged particle impact, kinematically complete experiments have been performed since 1969 (ref. 7). The theoretical analysis of such experiments was thought to yield a complete picture of the basic features of the collision process, at least for large collision energies. These conclusions are, however, almost exclusively based on studies of restricted electron-emission geometries. Here, we report three-dimensional images of the complete electron emission pattern for the single ionization of helium by the impact of C6+ ions of energy 100 MeV per a.m.u. (a four-body system) and observe features that have not been predicted by any published theoretical model. We propose a higher-order ionization mechanism, involving the interaction between the projectile and the target nucleus, to explain these features.

Journal Article↗

Effect of exercise mode on blood glucose disposal during physiological hyperinsulinaemia in humans.

The aim of this study was to compare whole-body glucose uptake in cycling and running performed during physiological hyperinsulinaemia. On three occasions, seven male subjects underwent a hyperinsulinaemic (30 mU m(-2) min(-1)), euglycaemic (5 mmol l(-1)) clamp for 120 min. On one occasion, subjects rested for the duration of the trial (CON). On the other two occasions, after an initial resting period of 30 min, subjects either cycled (CYC) or ran (RUN) for 90 min at 65% of maximal O(2) uptake (VO(2max)). Insulin infusion resulted in physiological hyperinsulinaemia that was maintained for the duration of each trial [CON: 61 (3) mU l(-1); CYC: 77 (7) mU l(-1); RUN: 77 (5) mU l(-1)]. The rate of glucose uptake was greater during RUN than during CYC [last 30 min of exercise: 140 (4) vs 109 (8) micromol kg(-1) min(-1), respectively; P <0.01]. A differential amount of active muscle mass and/or muscle fibre type recruitment might account for the observed differences in glucose disposal between cycling and running.

Adult↗

Triplane fractures of the distal tibia requiring open reduction and internal fixation. Pre-operative planning using computed tomography.

Computed tomography (CT) of triplane fractures provides useful information not available on conventional radiographs. Knowledge of the size and position of displaced fragments, the location of the intra-articular fracture and any associated articular incongruency is useful when undertaking pre-operative planning.A postal survey of surgeons revealed only 38% always requested CT scans before undertaking open reduction and internal fixation of displaced triplane fractures. Examples of the usefulness of CT scans in pre-operative planning is presented in two cases.

Fracture Fixation, Internal↗

Changes in zooxanthellae density, morphology, and mitotic index in hermatypic corals and anemones exposed to cyanide.

Sodium cyanide (NaCN) is widely used for the capture of reef fish throughout Southeast Asia and causes extensive fish mortality, but the effect of NaCN on reef corals remains debated. To document the impact of cyanide exposure on corals, the species Acropora millepora, Goniopora sp., Favites abdita, Trachyphyllia geoffrio, Plerogyra sp., Heliofungia actinformis, Euphyllia divisa, and Scarophyton sp., and the sea anemone Aiptasia pallida were exposed to varying concentrations of cyanide for varying time periods. Corals were exposed to 50, 100, 300, and 600 mg/l of cyanide ion (CN(-)) for 1-2 min (in seawater, the CN(-) forms hydrocyanic acid). These concentrations are much lower than those reportedly used by fish collectors. Exposed corals and anemones immediately retracted their tentacles and mesenterial filaments, and discharged copious amounts of mucus containing zooxanthellae. Gel electrophoreses techniques found changes in protein expression in both zooxanthellae and host tissue. Corals and anemones exposed to cyanide showed an immediate increase in mitotic cell division of their zooxenthellae, and a decrease in zooxanthellae density. In contrast, zooxanthellae cell division and density remained constant in controls. Histopathological changes included gastrodermal disruption, mesogleal degradation, and increased mucus in coral tissues. Zooxanthellae showed pigment loss, swelling, and deformation. Mortality occurred at all exposure levels. Exposed specimens experienced an increase in the ratio of gram-negative to gram-positive bacteria on the coral surface. The results demonstrate that exposure cyanide causes mortality to corals and anemones, even when applied at lower levels than that used by fish collectors. Even brief exposure to cyanide caused slow-acting and long-term damage to corals and their zooxanthellae.

Animals↗

Early outcome and cost-effectiveness of endoscopic versus open carpal tunnel release: a randomized prospective trial.

Proponents of endoscopic carpal tunnel release have been advocating the technique for more than 10 years but there is still debate about its efficacy, safety and cost-effectiveness. We have performed a randomized, prospective, blind trial to compare early outcome after single portal endoscopic or open carpal tunnel surgery and to assess the cost-effectiveness of the procedures. There were no significant differences in symptom and functional activity scores, grip strength or anterior carpal pain in the first 3 months. For those in employment, we found a statistically significant difference between the two treatment groups with the endoscopic group returning to work, on average, 8 (95% CI, 2-13 days) days sooner than the open group. This translates into a cost saving to industry. There were no major neurovascular complications in either group. On the basis of these findings, we recommend that endoscopic carpal tunnel release should be considered in the employed as a cost-effective procedure, but perhaps not in the general population as a whole.

Activities of Daily Living↗

Casein kinase ii (protein kinase ck2) regulates serotonin 5-ht(3) receptor channel function in ng108-15 cells.

We have used whole-cell recording techniques in the mouse neuroblastoma X rat glioma hybrid NG108-15 cell line to test whether protein kinase CK2 (CK2; also known as casein kinase II) modulates the function of the serotonin 5-HT(3) receptor (5-HT(3)R) channel. The rapid application of 5-HT (50 microM) to NG108-15 cells elicits a 5-HT(3)R-mediated inward current response that rapidly reaches peak amplitude and then desensitizes in the continued presence of agonist. Internal dialysis with CK2 (20 micrograms/ml) via the patch pipette significantly increases the amplitude and decreases the rate of desensitization of the 5-HT(3)R-mediated responses. CK2 that had been heat-inactivated has no effect on either the amplitude or the kinetics of desensitization of the 5-HT(3)R responses. These data suggest that dialysis with protein kinase CK2 significantly enhanced current through the 5-HT(3)R channel, and that CK2 may be an important regulator of 5-HT(3)R channel function in the nervous system, possibly serving to facilitate the 5-HT-induced excitation of the cells.

Animals↗

Cold weather nitrogen removal deficiencies of aerated lagoons.

Aerated lagoons are widely used throughout the state of Iowa, USA by small communities, due to their relatively low costs and maintenance requirements. Although aerated lagoons were not initially designed for ammonia removal many of these facilities have been assigned effluent ammonia limits in recent years Since widespread monitoring began, it has been found that aerated lagoons tend to have problems with high effluent ammonia concentrations during the winter and early spring. This study collected and analyzed data from 10 aerated lagoon facilities in central Iowa to determine the factors governing cold weather nitrogen removal in aerated lagoons. The factors found to affect performance were temperature and detention time. None of the following factors were found to significantly affect performance: dissolved oxygen (DO), pH, CBOD5 loading, total nitrogen loading, aerated cell depth and design standards governing the design. It should be noted that DO and pH were relatively constant and generally favorable for nitrification. Increased mixing energy was correlated with poorer performance, but this correlation may not be correct as the expected benefit of more intense mixing conditions may masked by the overwhelming benefit of long detention times.

Ammonia↗