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Biomedical subjects

R B Jones

Publications and source records attributed to R B Jones.

At least 37 records · Page 2Linked to original sources

Maillard reaction induced lactose attachment to bovine beta-lactoglobulin: electrospray ionization and matrix-assisted laser desorption/ionization examination.

Nonenzymatic attachment of lactose to beta-lactoglobulin (beta-Lg) was investigated under different conditions. Solubilized conditions, dry environment, and a combination of dry and solubilized environments, were examined for their effects on lactosylation. Temperatures ranging from 50 to 65 degrees C and time intervals between 1 h and 4 days were used. Electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry were implemented to examine the reaction products. Maximum attachment efficiency occurred at 65 degrees C held for 3 h in dry-way conditions. Incubations held for long periods of time under dry-way conditions suggest possible denaturation. Both ESI and MALDI data suggest beta-Lg removal in the solubilized samples held for long periods of time. A combination of solubilized and dry environments led to very similar mass spectrogram results over time.

Animals↗

Acute stimulation of glucose uptake by leptin in l6 muscle cells.

The adipocyte hormone, leptin, acts via the central nervous system to modulate glucose metabolism by skeletal muscle, but the direct effects of leptin on glucose metabolism by skeletal muscle are unclear. In this study, we have examined effects of leptin on glucose uptake by cultured L6 muscle cells assessed with the non-metabolised glucose analogue 2-deoxy-D-glucose. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis of RNA showed that L6 muscle cells express a short isoform of the leptin receptor (ObRa), but not the long isoform (ObRb). In the absence of added insulin, incubation of L6 muscle cells with murine leptin (10( -11)-10( -8) M) for 10 min and 1 h increased glucose uptake by 15 % - 23 %. This effect of leptin was lost by 4 h. Leptin (10( -10) - 10( -9) M) initially (after 10 min) suppressed insulin-stimulated glucose uptake by 14 - 16 %, but had no effect in the longer term. Leptin-stimulated glucose uptake was inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin, but not by the janus kinase-2 (JAK-2) inhibitor tyrphostin AG490. The results suggest that leptin can act directly on L6 muscle cellsvia a short leptin receptor isoform to acutely stimulate basal (but not insulin-stimulated) glucose uptake via a PI3K-dependent pathway.

Androstadienes↗

Pecking at other birds and at string enrichment devices by adult laying hens.

1. Bunches of white string (polypropylene twine) are particularly attractive pecking stimuli for both chicks and adult laying hens. Furthermore, these devices can retain the birds' interest over lengthy periods. It has also been demonstrated that birds with trimmed feathers elicit feather pecking. The present study was designed to determine whether string devices would retain their attractiveness in the presence of a competing stimulus: a trimmed hen. 2. Lohmann Brown hens were reared in 20 groups of 5 in floor pens with perches from 17 weeks of age. They were exposed to one of two treatments when they were 23 weeks old. One hen was removed from every pen and the feathers on her rump were trimmed. Immediately before her return two string devices were suspended from a perch in treatment 1 whereas no devices were included in treatment 2. Pecking behaviours were immediately observed for 30 min; this procedure was repeated later that day. The devices remained in the pens used in treatment 1 and these birds were observed again for 15 min after 14 d. 3. The string devices were pecked earlier and more than either the trimmed or untrimmed hens. Furthermore, the devices were still being pecked 2 weeks after their introduction. 4. The virtual absence of severe feather pecking and of aggressive head pecks precluded test of our hypothesis that the devices would divert potentially injurious pecking away from other birds. However, the fact that the birds showed sustained interest in the devices, even in the presence of a competing stimulus, supports our proposal that string may represent a practicable and effective form of environmental enrichment.

Animal Husbandry↗

Structural basis for interaction of FGF-1, FGF-2, and FGF-7 with different heparan sulfate motifs.

Stromal cell-derived FGF-7 binds and activates only the resident FGFR2IIIb in epithelial cells while FGF-1 and FGF-2 exhibit a broader interaction with multiple isoforms of FGFR. Here we report the structure of FGF-7 that has been solved to 3.1 A resolution by molecular replacement with the structure of a dual function chimera of FGF-7 and FGF-1 (FGF-7/1) which was resolved to 2.3 A. Comparison of the FGF-7 structure to that of FGF-1 and FGF-2 revealed the strongly conserved Calpha backbone among the three FGF polypeptides and the surface hydrophobic patch that forms the primary receptor-binding domain. In contrast, a decrease and dispersion of the positive surface charge density characterized the heparin-binding domain of FGF-7 defined by homology to that of FGF-1 and FGF-2 in complexes with heparin. A simple heparin hexasaccharide that cocrystallized with FGF-1 and FGF-2 and protected both against protease in solution failed to exhibit the same properties with FGF-7. In contrast to FGF-1 and FGF-2, protection of FGF-7 was enhanced by heparin oligosaccharides of increased length with those exhibiting a 3-O-sulfate being the most effective. Protection of FGF-7 required interaction with specifically the fraction of crude heparin retained on antithrombin affinity columns. Conversely, heparin enriched by affinity for immobilized FGF-7 exhibited anti-factor Xa activity similar to that purified on an antithrombin affinity matrix. In contrast, an FGF-1 affinity matrix enriched the fraction of crude heparin with low anti-factor Xa activity. The results provide a structural basis to suggest that the unique FGF-7 heparin-binding (HB) domain underlies a specific restriction in respect to composition and length of the heparan sulfate motif that may impact specificity of localization, stability, and trafficking of FGF-7 in the microenvironment, and formation and activation of the FGFR2IIIb kinase signaling complex in epithelial cells.

Amino Acid Sequence↗

5'- and 3'-terminal nucleotides in the FGFR2 ISAR splicing element core have overlapping roles in exon IIIb activation and exon IIIc repression.

The cell type-specific, mutually-exclusive alternative splicing of the fibroblast growth factor receptor 2 (FGFR2) pre-mRNA is tightly regulated. A sequence termed ISAR (intronic splicing activator and repressor) has been implicated as an important cis regulatory element in both activation of exon IIIb and repression of exon IIIc splicing in epithelial cells. In order to better understand how this single sequence could have dual roles, we transfected minigenes containing a series of 2-bp mutations in the 18 3'-most nucleotides of ISAR that we refer to as the ISAR core. Transfection of cells with dual-exon (IIIb and IIIc) minigenes revealed that mutation of terminal sequences of the core led to decreased exon IIIb inclusion and increased exon IIIc inclusion. Transfection of cells with single-exon IIIb minigenes and single-exon IIIc minigenes revealed that mutation of terminal sequences of the ISAR core led to decreased exon IIIb inclusion and increased exon IIIc inclusion, respectively. Nucleotides of the ISAR core responsible for exon IIIb activation appear to overlap very closely with those required for exon IIIc repression. We describe a model in which ISAR and a 5' intronic sequence known as IAS2 form a stem structure required for simultaneous exon IIIb activation and exon IIIc repression.

Alternative Splicing↗

Randomised trial of personalised computer based information for patients with schizophrenia.

OBJECTIVES: To compare use, effect, and cost of personalised computer education with community psychiatric nurse education for patients with schizophrenia. DESIGN: Randomised trial of three interventions. Modelling of costs of alternatives. PARTICIPANTS: 112 patients with schizophrenia in contact with community services; 67 completed the intervention. INTERVENTIONS: Three interventions of five educational sessions: (a) computer intervention combining information from patient's medical record with general information about schizophrenia; (b) sessions with a community psychiatric nurse; (c) "combination" (first and last sessions with nurse and remainder with computer). MAIN OUTCOME MEASURES: Patients' attendance, opinions, change in knowledge, and psychological state; costs of interventions and patients' use of NHS community services; modelling of costs for these three, and alternative, interventions. RESULTS: Rates of completion of intervention did not differ significantly (71% for combination intervention, 61% for computer only, 46% for nurse only). Computer sessions were shorter than sessions with nurse (14 minutes v 60 minutes). More patients given nurse based education thought the information relevant. Of 20 patients in combination group, 13 preferred the sessions with the nurse and seven preferred the computer. There were no significant differences between groups in psychological outcomes. Because of the need to transport patients to the computer for their sessions, there was no difference between interventions in costs, but computer sessions combined with other patient contacts would be substantially cheaper. CONCLUSIONS: The computer based patient education offered no advantage over sessions with a community psychiatric nurse. Investigation of computer use combined with other health service contacts would be worth while.

Adolescent↗

Clinical findings, consanguinity, and pedigrees in children with anophthalmos in southern India.

This study aimed to describe clinical findings, pedigrees, and possible environmental risk factors in children with clinical anophthalmos and remnant microphthalmos in either eye in southern India. Twenty-four children (14 male, 10 female; mean age 10.3 years, age range 1.3 to 18 years,) were recruited from schools for the blind, hospitals, and community-based rehabilitation programmes in Andhra Pradesh, India, over 1 year. Family members were examined, and mothers interviewed. Fifteen children had anophthalmos and nine had remnant microphthalmos in one or both eyes. Twelve children had associated systemic findings, of which six were major and six were minor abnormalities. Information on consanguinity was available in 19 children, 12 of whom had consanguineous parents. Five children had a positive family history. Two mothers had a history of night blindness, and one had a history of pesticide exposure during pregnancy. High rates of consanguinity suggest a genetic recessive aetiology.

Adolescent↗

Intensive chemotherapy for progressive chronic lymphocytic leukemia administered early after a nonmyeloablative allograft.

A 51-year-old patient with refractory CLL elected to participate in a trial of nonmyeloablative trans- plantation from an HLA-matched unrelated donor. He received low-dose fludarabine/TBI, with infusion of donor PBPC and cyclosporin (CsA)/MMF. Early post transplant he experienced explosive tumor growth with respiratory insufficiency. After immunosuppression discontinuation and rituximab administration, no response was observed. This prompted treatment with cyclophosphamide (2 g/m(2)/day x 2), paclitaxel (250 mg/m(2) over 24 h), doxorubicin (50 mg/m(2)), solumedrol (500 mg/day), and a second dose of rituximab, from days +11 to +14. A rapid response was achieved. Chemotherapy did not cause an obvious compromise of donor stem cell engraftment or establishment of stable donor chimerism.

Anti-Bacterial Agents↗

Sibutramine metabolites increase glucose transport by cultured rat muscle cells.

BACKGROUND: The anti-obesity agent sibutramine, a serotonin and noradrenaline reuptake inhibitor (SNRI), has been shown to reduce insulin resistance and improve glycaemic control in obese-diabetic ob/ob mice and overweight type 2 diabetic patients. OBJECTIVE: To investigate whether sibutramine or its metabolites act directly on muscle cells to improve glucose uptake and insulin action. DESIGN: Uptake of the non-metabolized glucose analogue 2-deoxyglucose was measured in cultured L6 rat muscle cells after incubation with sibutramine, its two pharmacologically active metabolites and related agents. RESULTS: Sibutramine itself (10(-8)-10(-6) M) did not significantly affect 2-deoxyglucose uptake during incubations up to 72 h. The primary amine metabolite M2 (10(-7) and 10(-6) M) increased basal and insulin-stimulated 2-deoxyglucose uptake (by 12% and 34%) after 24 h incubation. These effects of M2 were lost by 72 h incubation. However, the secondary amine metabolite M1 (10(-6) M) increased basal and insulin-stimulated 2-deoxyglucose uptake (by 50%) after 72 h incubation, although M1 was ineffective after 24 h. M2 stimulated 2-deoxyglucose uptake in the presence of LY-294,002 (an inhibitor of phosphatidylinositol 3-kinase) but the effect of M2 was inhibited by cytochalasin B, which acutely blocks glucose transporters. Incubations with serotoninergic, noradrenergic and dopaminergic agents, or agents known to stimulate release or inhibit reuptake of these substances in nervous tissues indicated that the sibutramine metabolites were not affecting 2-deoxyglucose uptake via mechanisms associated with their SNRI properties. CONCLUSIONS: Sibutramine metabolites can improve insulin-sensitive 2-deoxyglucose uptake by cultured muscle cells independently of SNRI effects.

Animals↗

The clinician's role in meeting patient information needs: suggested learning outcomes.

BACKGROUND: Patients have always fulfilled their information needs from a variety of different sources over time. Clinician-patient consultations are one part of that process. Some patients have increasing opportunities to obtain information through new sources such as the internet, touch-screens, and patient-held records. Others remain poorly informed. OBJECTIVES: To identify learning outcomes for clinicians in meeting patient information needs and working with well-informed patients. DESIGN: Four-stage multicentre multidisciplinary qualitative study. SETTING AND SUBJECTS: (1) Semistructured interviews with 20 clinicians in Glasgow; (2) semistructured interviews with 52 clinicians in Nottingham and London; (3) testing of consensus by postal questionnaire and Delphi method amongst 37 clinicians in medicine, nursing and the professions allied to medicine, and (4) conference to discuss results. RESULTS: 46 learning outcomes were identified in the eight areas of: placing a higher priority on patient information and education; understanding the patient's information needs and environment; understanding the emotional aspects of learning; developing patient understanding; helping patients to understand about health care and health care information; learning from the patient; knowing about information sources and their use, and issues of multidisciplinary working. CONCLUSIONS: The suggested learning outcomes provide the basis for wider discussion, for possible inclusion in curricula both at undergraduate and continuing education levels, and as the basis for the development of new educational materials.

Communication↗

Tonsillar metastasis: A rare presentation of gastric carcinoma.

Metastatic carcinoma of the tonsil is uncommon. Tonsillar metastases rarely become apparent before the diagnosis of the primary neoplasm. We describe only the second reported case of tonsillar metastasis as a presenting feature of gastric carcinoma. A review of the literature is also discussed.

Aged↗

Does occasional movement make pecking devices more attractive to domestic chicks?

1. Previous studies have shown that a bunch of string is a particularly attractive pecking stimulus for chicks and adult laying hens. Because movement is thought to be an important attribute of enrichment objects, this study determined whether occasional movement would affect the attractiveness of this device. 2. In experiment 1 the responses of pair-housed chicks to string were compared when devices in adjacent cages were either linked (so that pecking or pulling at the string in one cage moved the adjoining one) or not (separate). In experiment 2 the devices in half the cages were jigged remotely by the experimenter whereas the others remained static. In both cases, the string devices were introduced into the cages for 10 min on each of 5 consecutive days. 3. No treatment effects were apparent in experiment 1 when pooled data was analysed but comparison of responses on days 1 and 5 revealed that only the chicks presented with non-linked devices showed increased interest with repeated exposure. 4. Chicks given static devices in experiment 2 pecked sooner, more often and longer at them than did those exposed to similar ones that were jigged regularly by the experimenter. Jigged devices attracted slightly more pecking with repeated exposure, which may have reflected familiarity-induced fear-reduction, but chick responses showed no apparent changes from day 2 onwards. Conversely, rather than showing habituation, the chicks pecked progressively more at the static devices with repeated presentation. 5. The present results show that chicks pecked readily at bunches of white string, thus confirming its attractive properties but that static devices were more attractive than those incorporating occasional movement. These and previous findings are discussed in terms of their implications for the development of effective environmental enrichment.

Animal Feed↗

Age-related changes in fear, sociality and pecking behaviours in two strains of laying hen.

1. Two lines of commercial hybrid layers (Tetra and ISA Brown) were reared from hatch to 30 weeks of age in groups of 8. The objectives of the experiment were to evaluate the significance of the different selection practices involved in the development of the lines and to assess the potential association between selected behavioural states and the potential for feather damage and cannibalism. 2. Behavioural tests related to fear (tonic immobility, novel object, open field), sociality (runway, proximity in the home pen) and pecking (feather bunch and focal observations of inter-bird and environmental pecking) were conducted at 0 to 2, 5 to 7, 12 to 14, 19 to 21 and 29 to 31 weeks of age. Scan sampling of general behaviour was also conducted at these ages. 3. Underlying sociality was greater in Tetras than in ISA Brown hens. 4. There were no apparent overall strain differences in fearfulness although ISA Brown hens showed significantly longer tonic immobility fear reactions than Tetras at 31 weeks of age. 5. ISA Brown hens gave and received more gentle pecks than Tetra hens whereas preening was commoner among Tetras. There were no strain differences in the number of pecks at litter or food. 6. As birds aged they showed less avoidance of novel objects and Tetras, though not ISA Browns, showed progressively shorter tonic immobility responses. Birds of both strains spent less time resting, more foraging (pecking and scratching) and pecked more at the feather bunch at older ages. 7. Measures taken in the TI, open field, runway (social affiliation) and feather bunch tests were stable over time whereas focal observations of pecking at hens and the environment were not. 8. Factor Analysis showed that 3 factors defined by the novel object test, environmental pecking and pecking ata feather bunch explained most of the variation in the correlation matrix between summary measures for the 8 behavioural traits.

Age Factors↗

Incidence of and risk factors for diabetic retinopathy in diabetic clinic attenders.

The incidence and risk factors for the development of diabetic retinopathy during a mean (SD) follow-up period of 4.6 (2.9) (range 1-12.4) years have been examined among 3424 patients (1878 males and 1546 females) with diabetes mellitus from three outpatient clinics at the University Hospital, Nottingham. The mean (SD) age of participants was 49.2 (17.9) years with a mean (SD) duration of diabetes of 7.3 (9.0) years at initial registration. Among the 3424 patients free of retinopathy at initial registration who attended the clinic at least twice in the period 1979-1992, the incidence of any retinopathy was 59.6 (57.8 male and 61.8 female) per 1000 person-years based on 15,571 person-years of follow-up. The incidence rate of retinopathy was 72% higher among insulin-treated than among non-insulin-treated noninsulin-dependent diabetes mellitus (NIDDM) clinic attenders. Using a Cox's Proportional Hazards Model for insulin-dependent diabetes (IDDM) and NIDDM (insulin and non-insulin-treated) diabetes separately, longer duration of diabetes, higher systolic blood pressure and poor metabolic control were significant independent predictors of retinopathy for all three groups. Never smoking was a significant independent predictor of retinopathy for the insulin-dependent diabetes groups. Lower body mass index, proteinuria and age were predictors of retinopathy only for non-insulin-treated NIDDM patients. Gender and creatinine had no significant independent association with retinopathy when other covariates were considered. These findings will help the identification of those patients at particular risk of retinopathy so that clinic time for screening of eyes can be appropriately focused.

Ambulatory Care Facilities↗

Multicenter evaluation of the BDProbeTec ET System for detection of Chlamydia trachomatis and Neisseria gonorrhoeae in urine specimens, female endocervical swabs, and male urethral swabs.

The performance of the Becton Dickinson BDProbe Tec ET System Chlamydia trachomatis and Neisseria gonorrhoeae Amplified DNA Assays (BD Biosciences, Sparks, Md.) was evaluated in a multicenter study. Specimens were collected from 2,109 men and women, with or without symptoms, attending sexually transmitted disease, family planning, and obstetrics and gynecology clinics. Both swab and urine samples were collected, and the results obtained from 4,131 specimens were compared to those from culture and the LCx nucleic acid amplification test (Abbott Industries, Abbott Park, Ill.). PCR and cytospin of the culture transport medium with chlamydia direct fluorescent antibody staining were used to adjudicate chlamydia culture-negative results. Sensitivity and specificity were calculated both with and without use of the amplification control (AC), with little apparent difference in the results. Without the AC result, sensitivity for C. trachomatis and N. gonorrhoeae were 92.8 and 96.6%, respectively, for cervical swabs and 80.5 and 84.9% for urine from women. C. trachomatis and N. gonorrhoeae sensitivities were 92.5 and 98.5%, respectively, for male urethral swabs and 93.1 and 97.9% for urine from men. This amplified DNA system for simultaneous detection of chlamydial and gonococcal infections demonstrated superior sensitivity compared to chlamydia culture and has performance characteristics comparable to those of other commercially available nucleic acid-based assays for these organisms.

Cervix Uteri↗

Enhancing the specificity of the COBAS AMPLICOR CT/NG test for Neisseria gonorrhoeae by retesting specimens with equivocal results.

The COBAS AMPLICOR CT/NG test for Neisseria gonorrhoeae cross-reacts with certain strains of nonpathogenic Neisseria species. In some strains, the target sequence is identical to that of N. gonorrhoeae, whereas other strains have a small number of mismatches within the regions recognized by the primers or probe used in the COBAS AMPLICOR NG test. These cross-reactive strains are occasionally present in urogenital specimens, causing false-positive results in the COBAS AMPLICOR NG test. Analysis of the data generated in a large multicenter clinical trial showed that 2.9% of the specimens gave signals between A(660)s of 0.2 and 3.5 but that one-half of these equivocal specimens did not contain N. gonorrhoeae. Most of these equivocal specimens were correctly classified as true positive or true negative by retesting in duplicate and defining a PCR-positive result as two of three results with an A(660) of > or =2.0. If specimens had been classified as positive or negative based on a single test result using a cutoff of an A(660) of 0.2, specificity would have ranged from 96.2 to 98.9% depending on specimen type, sex, and presence of symptoms. By employing the equivocal zone-retesting algorithm, specificity increased to 98.6 to 99.9% with little effect (0.1 to 4.9% decrease) on sensitivity in most specimen types, enabling the test to achieve a positive predictive value of at least 90% in populations with a prevalence of 4% or higher. In lower-prevalence populations, the test could be used to screen for presumptive infections that would have to be confirmed by an independent test.

Adult↗