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Biomedical subjects

Gareth Jones

Publications and source records attributed to Gareth Jones.

At least 37 records · Page 2Linked to original sources

Isolation and characterization of CXC receptor genes in a range of elasmobranchs.

The CXC group of chemokines exert their cellular effects via the CXCR group of G-protein coupled receptors. Six CXCR genes have been identified in humans (CXCR1-6), and homologues to some of these have been isolated from a range of vertebrate species. Here we isolate and characterize CXCR genes from a range of elasmobranch species. One CXCR1/2 gene fragment isolated from Scyliorhinus caniculus (lesser spotted catshark), and two CXCR1/2 copies from each of the elasmobranchs, Cetorhinus maximus (basking shark), Carcharodon carcharias (great white shark), and Raja naevus (cuckoo ray), exhibit high similarity to both CXCR1 and CXCR2. The two copies evident in the cuckoo ray and lamniform sharks provide strong evidence of CXCR1/2 lineage specific duplication in rays and sharks. A CXCR fragment isolated from Lamna ditropis (salmon shark) shows high similarity to a range of CXCR4 genes and strong clustering with CXCR4 gene homologues was apparent during phylogenetic reconstruction.

Amino Acid Sequence↗

Echolocation call intensity in the aerial hawking bat Eptesicus bottae (Vespertilionidae) studied using stereo videogrammetry.

Aerial hawking bats use intense echolocation calls to search for insect prey. Their calls have evolved into the most intense airborne animal vocalisations. Yet our knowledge about call intensities in the field is restricted to a small number of species. We describe a novel stereo videogrammetry method used to study flight and echolocation behaviour, and to measure call source levels of the aerial hawking bat Eptesicus bottae (Vespertilionidae). Bats flew close to their predicted minimum power speed. Source level increased with call duration; the loudest call of E. bottae was at 133 dB peSPL. The calculated maximum detection distance for large flying objects (e.g. large prey, conspecifics) was up to 21 m. The corresponding maximum echo delay is almost exactly the duration of one wing beat in E. bottae and this also is its preferred pulse interval. These results, obtained by using videogrammetry to track bats in the field, corroborate earlier findings from other species from acoustic tracking methods.

Animals↗

Managing authenticity: the paradox of great leadership.

Leaders and followers both associate authenticity with sincerity, honesty, and integrity. It's the real thing--the attribute that uniquely defines great managers. But while the expression of a genuine self is necessary for great leadership, the concept of authenticity is often misunderstood, not least by leaders themselves. They often assume that authenticity is an innate quality--that a person is either genuine or not. In fact, the authors say, authenticity is largely defined by what other people see in you and, as such, can to a great extent be controlled by you. In this article, the authors explore the qualities of authentic leadership. To illustrate their points, they recount the experiences of some of the authentic leaders they have known and studied, including the BBC's Greg Dyke, Nestlé's Peter Brabeck-Letmathe, and Marks & Spencer's Jean Tomlin. Establishing your authenticity as a leader is a two-part challenge. You have to consistently match your words and deeds; otherwise, followers will never accept you as authentic. But it is not enough just to practice what you preach. To get people to follow you, you also have to get them to relate to you. This means presenting different faces to different audiences--a requirement that many people find hard to square with authenticity. But authenticity is not the product of manipulation. It accurately reflects aspects of the leader's inner self, so it can't be an act. Authentic leaders seem to know which personality traits they should reveal to whom, and when. Highly attuned to their environments, authentic leaders rely on an intuition born of formative, sometimes harsh experiences to understand the expectations and concerns of the people they seek to influence. They retain their distinctiveness as individuals, yet they know how to win acceptance in strong corporate and social cultures and how to use elements of those cultures as a basis for radical change.

Commerce↗

Treatment of idiopathic membranoproliferative glomerulonephritis with mycophenolate mofetil and steroids.

BACKGROUND: Treatment of adults with idiopathic membranoproliferative glomerulonephritis (IMPGN) is often unrewarding with approximately 60% of patients progressing to end-stage renal failure within 10 years. Although children with IMPGN may respond to steroid therapy, there is no significant benefit to treating adult IMPGN patients with immunosuppression. METHODS: Outcome measures in five patients with IMPGN who were treated with oral prednisolone and mycophenolate mofetil (MMF) (treatment group) were compared with six patients with IMPGN who did not receive immunosuppression (control group). RESULTS: There was no significant difference between either group in baseline clinical characteristics or systolic and diastolic blood pressure during observation. In the treatment group, there was a significant reduction in proteinuria from a baseline of 5.09 to 1.97 g/24 h (P = 0.003) at 6 months, 1.96 g/24 h (P = 0.003) at 12 months and 2.59 g/24 h (P = 0.015) at 18 months. There was no significant change in proteinuria over 18 months in the control group. Serum creatinine concentration and creatinine clearance did not change significantly over 18 months in the treatment group. In the control group, there were significant changes in serum creatinine and creatinine clearance over 18 months [baseline 103 to 159 micromol/l (P = 0.004) and baseline 108 to 67 ml/min (P > 0.001), respectively] when compared to baseline, although the differences were not significant when the two groups were compared directly. CONCLUSIONS: This preliminary study suggests that in the short term, the combination of MMF and prednisolone can significantly reduce proteinuria and may preserve renal function in patients with IMPGN.

Adrenal Cortex Hormones↗

CD12: a new high-flux beamline for ultraviolet and vacuum-ultraviolet circular dichroism on the SRS, Daresbury.

This paper describes the commissioning and characterization of an SRS bending-magnet beamline constructed for the measurement of vacuum-ultraviolet circular dichroism on biological and other materials. The beamline provides photon fluxes of many orders of magnitude greater than commercial instruments or beamlines at other synchrotron radiation facilities. The beamline uses the conventional approach of utilizing the plane polarized light emitted from the bending magnet which is subsequently converted into circularly polarized light using a photoelastic modulator with a switching frequency of 50 kHz. The beamline has a best wavelength resolution of 0.5 nm and stray light levels better than 0.01%. The latter may be predicted to give improved performance over other beamlines at synchrotron radiation sources especially when short-wavelength CD spectra are to be collected. An example spectrum and submillisecond time-resolved CD profile are given and the impact that the new beamline is likely to have is speculated on. The ultimate flux limitations of the technique with regard to the avoidance of the effects of radiation damage are also discussed.

Circular Dichroism↗

HIV type 1-specific inter- and intrasubtype cellular immune responses in HIV type 1-infected Ugandans.

Investigations concerning the extent and nature of subtype-specific and intersubtype immune responses in HIV-1-infected persons are necessary for the development of appropriate candidate vaccines. In the cross-sectional study described here, 26 HIV-1-positive Ugandan patients were tested for their ability to mount HIV antigen-specific cellular immune responses. Subjects were infected with either HIV-1 subtypes A, C, or D. Recombinant vaccinia virus (rVV)-based and peptide-based enzyme-linked immunospot (Elispot) assays were used to evaluate HIV-1-specific gamma-interferon (IFN-gamma) cellular responses. rVV expressing gag, pol, or env proteins derived from HIV-1 subtypes A, B, and D were evaluated for their ability to induce whole HIV-1-protein-specific IFN-gamma responses in 14 patients. A panel of previously identified HLA class I-restricted peptides based on representative sequences from HIV-1 subtypes A, B, C, and D and restricted through HLA-A2, -A29, -B42, -B53, and -B57 alleles were used to evaluate the presence of HIV-1-peptide-specific T cells in 19 patients. Using rVV, 27 of a possible 38 subtype-specific responses (71%) and 56 of a possible 110 intersubtype responses (51%) were observed. When appropriate peptides were used 18 of 39 (46.2%) subtype-specific and 13 of 39 (33.3%) intersubtype responses were observed. Peptide responses were higher quantitatively than those seen when rVV were used. In 7 patients, both rVV and specific peptides were evaluated; in 3 of 7 individuals, global responses were seen despite a lack of measurable HLA-restricted peptide-specific responses demonstrating the need to evaluate a broader range of HIV-specific immune responses.

Acquired Immunodeficiency Syndrome↗

How many child deaths can we prevent this year?

This is the second of five papers in the child survival series. The first focused on continuing high rates of child mortality (over 10 million each year) from preventable causes: diarrhoea, pneumonia, measles, malaria, HIV/AIDS, the underlying cause of undernutrition, and a small group of causes leading to neonatal deaths. We review child survival interventions feasible for delivery at high coverage in low-income settings, and classify these as level 1 (sufficient evidence of effect), level 2 (limited evidence), or level 3 (inadequate evidence). Our results show that at least one level-1 intervention is available for preventing or treating each main cause of death among children younger than 5 years, apart from birth asphyxia, for which a level-2 intervention is available. There is also limited evidence for several other interventions. However, global coverage for most interventions is below 50%. If level 1 or 2 interventions were universally available, 63% of child deaths could be prevented. These findings show that the interventions needed to achieve the millennium development goal of reducing child mortality by two-thirds by 2015 are available, but that they are not being delivered to the mothers and children who need them.

Child, Preschool↗

IL-13-induced changes in the goblet cell density of human bronchial epithelial cell cultures: MAP kinase and phosphatidylinositol 3-kinase regulation.

In addition to a direct proinflammatory role, IL-13 has been demonstrated to induce a goblet cell metaplastic phenotype in the airway epithelium in vivo. We have studied the direct effects of IL-13 (and IL-4) on well-differentiated, air-liquid interface cultures of human bronchial epithelial cells (HBEs) and provide a quantitative assessment of the development of a mucus hypersecretory phenotype induced by these cytokines. Using Alcian blue staining of goblet cells and immunohistochemical detection of MUC5AC, we found that IL-13 (and IL-4) induced increases in the goblet cell density (GCD) of the HBE cultures. The effects of these cytokines were critically dependent on concentration: 1 ng/ml routinely induced a 5- to 10-fold increase in GCD that was associated with a hypersecretory ion transport phenotype. Paradoxically, 10 ng/ml of either cytokine induced a profound reduction in GCD. Removal of EGF from the culture media or treatment of the cells with AG-1478 [a potent inhibitor of EGF receptor tyrosine kinase (EGFR-TK)] demonstrated that the EGFR-TK pathway was key to the regulation of the basal GCD but that it was not involved in the IL-13-driven increase. The IL-13-driven increase in GCD was, however, sensitive to inhibition of MEK (PD-98059, U-0126), p38 MAPK (SB-202190), and phosphatidylinositol (PtdIns) 3-kinase (LY-294002). These data support the concept that IL-13 is in part able to induce a mucus hypersecretory phenotype through a direct interaction with the airway epithelium and that MAP kinase and PtdIns 3-kinase signaling pathways are involved.

Bronchi↗

Annual mortality rates and excess deaths of children under five in Iraq, 1991-98.

Data from two parallel household surveys conducted in Iraq by UNICEF in 1999 show that under-5 mortality declined steadily from 1974 to 1990, reaching about 63 per 1,000 live births in the period 1986-90. It then rose dramatically to 118 per 1,000 in 1991, the year of the Gulf War. The number of 'excess' under-5 deaths (i.e., the number in excess of the number predicted from past trends) in Iraq between 1991 and 1998 was calculated assuming that, instead of the rates measured by the 1999 survey for this period, either (a) average mortality rates for the period 1986-90 had been maintained, or (b) mortality had continued to decline at the rate observed between 1974 and 1990. According to these calculations, the estimated number of excess deaths resulting from the Gulf War and its aftermath up to 1998 was between 400,000 (assumption a) and 500,000 (assumption b).

Child, Preschool↗

Treatment of lower ureteral stones using the Dornier Compact Delta lithotripter.

BACKGROUND AND PURPOSE: Lithotripsy using new-generation machines requires minimal anesthesia and so can easily be given in an outpatient setting. We report our experience with the Dornier Compact Delta lithotripter in the primary management of lower ureteral stones. PATIENTS AND METHODS: We identified 128 patients treated with SWL for lower-ureteral stones between April 1999 and August 2001. Complete follow-up was available for 112 patients. Their ages ranged from 19 to 78 years, with women accounting for 23%. Only three patients had a ureteral stent in situ. All patients were routinely followed up at 2 weeks with a plain film. The timing of further follow-up depended on the initial response to treatment. RESULTS: Fragmentation occurred in 83 of 112 stones (74%): 93% of the successful cases and 43% of the unsuccessful ones. A total of 59 patients (53%) were stone free after one treatment. This figure increased to 73 (65%) after a second treatment. The mean size of the successfully treated stones was less than that of the failed stones (7.6 v 8.7 mm), although the difference did not reach statistical significance. Stone-free rates decreased as stone size increased, being 71% for the 28 stones < or =5 mm in diameter, 65% for the 52 stones 6 to 9 mm, 64% for the 25 stones 10 to 14 mm, and 42% for the 7 stones > or =15 mm. CONCLUSIONS: When SWL can be delivered promptly in an outpatient setting, it remains a useful first-line treatment for lower ureteral stones. Although it is not as effective as ureteroscopy, its use can avert the need for more invasive treatment in half to two thirds of patients. It should be limited to stones <15 mm.

Adult↗

The influence of flight speed on the ranging performance of bats using frequency modulated echolocation pulses.

Many species of bat use ultrasonic frequency modulated (FM) pulses to measure the distance to objects by timing the emission and reception of each pulse. Echolocation is mainly used in flight. Since the flight speed of bats often exceeds 1% of the speed of sound, Doppler effects will lead to compression of the time between emission and reception as well as an elevation of the echo frequencies, resulting in a distortion of the perceived range. This paper describes the consequences of these Doppler effects on the ranging performance of bats using different pulse designs. The consequences of Doppler effects on ranging performance described in this paper assume bats to have a very accurate ranging resolution, which is feasible with a filterbank receiver. By modeling two receiver types, it was first established that the effects of Doppler compression are virtually independent of the receiver type. Then, used a cross-correlation model was used to investigate the effect of flight speed on Doppler tolerance and range-Doppler coupling separately. This paper further shows how pulse duration, bandwidth, function type, and harmonics influence Doppler tolerance and range-Doppler coupling. The influence of each signal parameter is illustrated using calls of several bat species. It is argued that range-Doppler coupling is a significant source of error in bat echolocation, and various strategies bats could employ to deal with this problem, including the use of range rate information are discussed.

Acceleration↗

Mysterious Mystacina: how the New Zealand short-tailed bat (Mystacina tuberculata) locates insect prey.

The New Zealand short-tailed bat Mystacina tuberculata evolved in the absence of terrestrial mammals and initially with few potential predators. Unusual among bats, it is well adapted for the capture of prey on the ground. Bats from Fiordland, New Zealand had relatively low wing loadings and aspect ratios adapted for flight in cluttered habitats. We predicted that M. tuberculata would locate prey in air (uncluttered space) by echolocation. Echolocation call sequences associated with prey capture (terminal buzzes) were heard in the field, and bats detected and localized prey suspended on fishing line by echolocation in a flight cage. The bats emitted brief, multiharmonic echolocation calls at low duty cycle during search phase, and 64% of calls contained most energy in the fundamental harmonic. Approach- and terminal-phase calls were also broadband and multiharmonic. We predicted that bats would not use echolocation to locate prey hidden on the ground in leaf litter (cluttered space). Bats seemed unable to locate hidden prey precisely from the air and instead hunted for such prey while crawling. Echolocation calls were emitted at a low repetition rate on the ground, suggesting that here echolocation was used for orientation and not for prey detection. We experimentally removed cues available to the bats and showed that bats located mealworms in leaf litter by listening for prey-generated noises and possibly by olfaction.

Animals↗

Interleukin-13 induces a hypersecretory ion transport phenotype in human bronchial epithelial cells.

Interleukin (IL)-13 has been associated with asthma, allergic rhinitis, and chronic sinusitis, all conditions where an imbalance in epithelial fluid secretion and absorption could impact upon the disease. We have investigated the effects of IL-13 on the ion transport characteristics of human bronchial epithelial cells cultured at an apical-air interface. Ussing chamber studies indicated that 48 h pretreatment with IL-13 or IL-4 significantly reduced the basal short-circuit current (I(sc)) and inhibited the amiloride-sensitive current by >98%. Furthermore, the I(sc) responses were increased by more than six- and twofold over control values when stimulated with UTP or forskolin, respectively, after cytokine treatment. The IL-13-enhanced response to UTP/ionomycin was sensitive to bumetanide and DIDS and was reduced in a low-chloride, bicarbonate-free solution. Membrane permeablization studies indicated that IL-13 induced the functional expression of an apical Ca(2+)-activated anion conductance and that changes in apical or basolateral K(+) conductances could not account for the increased I(sc) responses to UTP or ionomycin. The results indicate that IL-13 converts the human bronchial epithelium from an absorptive to a secretory phenotype that is the result of loss of amiloride-sensitive current and an increase in a DIDS-sensitive apical anion conductance.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗