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Biomedical subjects

C Steel

Publications and source records attributed to C Steel.

At least 19 recordsLinked to original sources

Radiographic evaluation of sclerosis of the third carpal bone associated with exercise and the development of lameness in Standardbred racehorses.

REASONS FOR PERFORMING STUDY: Sclerosis of the third carpal bone is a common radiographic finding in both lame and sound racehorses, but there are no guidelines correlating degree of sclerosis and incidence of lameness. OBJECTIVES: To develop a protocol for describing subchondral bone sclerosis in C3 on dorsoproximal-dorsodistal oblique (DPr-DDiO) radiographs of the carpus and to correlate these changes with exercise history and carpal lameness. METHODS: One hundred and six Standardbreds entering their first year of training (exercise group) and 7 age-matched Standardbreds at pasture (controls) were examined at approximately 3 month intervals over 12-18 months. Examinations consisted of lameness evaluation and carpal radiographs (DPr-DDiO and flexed lateromedial projections). A grading system (very mild, mild, moderate and severe) for C3 sclerosis seen on the DPr-DDiO radiograph was developed that utilised a combination of the criteria of trabecular thickening (trabecular score; TS) and total percent area of the C3 radial facet affected (TAA). RESULTS: Exercise group horses showed significant increase in TS and TAA throughout training compared to control horses. Middle carpal joint lameness developed in 32/106 (30%) exercise group horses and none of the control horses. Incidence of middle carpal joint (MCJ) lameness was lower in horses with mild (2/30, 6.7%) than moderate (10/32, 31.2%) and severe (20/44, 45.4%) sclerosis throughout training. CONCLUSIONS: Horses with higher grades of sclerosis, as defined by this novel grading system, were more likely to develop MCJ lameness at some point of training. The proposed grading system gave a quantitative assessment of radiographic sclerosis that could then be used to correlate increasing severity of sclerosis with increasing incidences of lameness. POTENTIAL RELEVANCE: These results serve as a basis for further investigation into determining the degree of C3 sclerosis at which pathological changes and lameness can be expected.

Animals↗

Distractor cueing effects on choice reaction time and their relationship with schizotypal personality.

BACKGROUND AND OBJECTIVES: Although usually displaying increased distractibility, schizophrenic patients sometimes show a reduced influence of distractors during selective attention tasks. This study explored whether reduced distractor processing effects can also occur in healthy individuals with high levels of schizotypal personality traits. DESIGN AND METHOD: In all, 36 healthy volunteers completed schizotypal personality scales and a choice reaction time (RT) task in which they responded to the central letter of triads (XMX, YCY), ignoring the flanking distractors. RT increases on low-probability probe trials (YMY, XCX) measured distractor processing ('the distractor cueing effect'). Correlations between schizotypy scores and distractor cueing were evaluated. RESULTS: Healthy participants with high positive schizotypy scores (i.e. those reporting more hallucination-like experiences and delusion-like beliefs) showed smaller distractor cueing effects than those with lower scores. This association was independent of the influence of other schizotypal personality traits (disorganized, negative or asocial schizotypy) and was significant only for right-hand responses. These findings closely parallel the previously reported reduced distractor cueing effect, for right-hand responses, among acute-phase schizophrenic patients. CONCLUSION: Finding reduced distractor cueing effects in healthy participants with high levels of positive schizotypy increases confidence that reduced distractor cueing is a specific feature, rather than a non-specific consequence, of acute-phase schizophrenia.

Adult↗

Neuroimaging correlates of negative priming.

Many theoretical accounts of selective attention and memory retrieval include reference to active inhibitory processes, such as those argued to underlie the negative priming effect. fMRI was used in order to investigate the areas of cortical activation associated with Stroop interference, Stroop facilitation and Stroop negative priming tasks. The most significant activation within the negative priming task was within the inferior parietal lobule, left temporal lobe and frontal lobes. Areas of cortical activation are discussed with reference to theoretical accounts of the negative priming effect.

Adult↗

Evolution of immunologic responsiveness of persons living in an area of endemic bancroftian filariasis: a 17-year follow-up.

On an island in which bancroftian filariasis is endemic, 29 microfilaremic and 16 "endemic normal" (EN) subjects initially studied in 1974-1975 were reevaluated 17 years later. Eleven persons remained microfilaremic, whereas 18 had cleared both microfilaremia and antigenemia. Despite decreased infection on the island, antibody levels remained relatively constant for the subjects with persistent microfilaremia (Mf(+/+)), in contrast to sharp decreases for both EN subjects and subjects with cleared microfilaremia (Mf(+/-)). Although clinically indistinguishable from the EN subjects, the Mf(+/-) group had antibody levels (IgG, IgG4, and IgE) significantly lower than those of the EN subjects. Lymphocyte responses to parasite antigens were marginally greater in Mf(+/-) than in Mf(+/+) subjects, but both groups remained less cell responsive (as measured by proliferation, interleukin-5, interleukin-10, interferon-gamma, and granulocyte-macrophage colony-stimulating factor) than did the EN subjects. These findings suggest that, for microfilaremic persons, complete clearance of infection is not sufficient to restore "normal" immune responsiveness; filarial infection may induce very long-term deficits in the ability to respond to parasite antigens.

Adult↗

Testis ecdysiotropin, an insect gonadotropin that induces synthesis of ecdysteroid.

Testes of lepidoptera synthesized ecdysteroid in a somewhat different temporal pattern than the prothoracic glands that release ecdysteroid to the hemolymph. Brain extracts from Heliothis virescens and Lymantria dispar induced testes to synthesize ecdysteroid, but did not affect prothoracic glands. The testis ecdysiotropin (LTE) was isolated from L. dispar pupal brains by a series of high-pressure chromatography steps. Its sequence was Ile-Ser-Asp-Phe-Asp-Glu-Tyr-Glu-Pro-Leu-Asn-Asp-Ala-Asp-Asn-Asn-Glu-Val-Leu-Asp-Phe-OH, of molecular mass 2,473 Daltons. The predominant signaling pathway for LTE was via G(i) protein, IP3, diacylglycerol and PKC; a modulating pathway, apparently mediated by an angiotensin II-like peptide, was controlled via G(s) protein, cAMP, and PKA. Testis ecdysteroid caused isolated testis sheaths to also synthesize a growth factor that induced development of the male genital tract. The growth factor appeared to be a glycoprotein similar to vertebrate alpha-1-glycoprotein. A polyclonal antibody to LTE indicated LTE-like peptide in L. dispar brain medial neurosecretory cells, the suboesophageal, and other ganglia, and also in its target organ, the testis sheath. LTE immunoreactivity was also seen in testis sheaths of Rhodnius prolixus. LTE-like immunoactivity was also detected in developing optic lobes, antennae, frontal ganglia, and elongating spermatids of developing L. dispar pupae. This may indicate that LTE has a role in development as well as stimulation of testis ecdysteroid synthesis. Published 2001 Wiley-Liss, Inc.

Amino Acid Sequence↗

Two routes to [11C-carbonyl]organo-isocyanates utilizing [11C]phosgene ([11C]organo-isocyanates from [11C]phosgene).

Two generic radiosynthetic routes for the preparation of [11C-carbonyl]isocyanates have been developed. Reaction of N-organo-sulfinylamines; RNSO, (R = Me, Et, allyl, cyclohexyl and phenyl) with [11C]phosgene gave the corresponding [11C-carbonyl]isocyanates in good radiochemical yield (53-68%) from [11C]phosgene (decay corrected) in ca 16 min from EOB. Alternatively, the reaction of [11C]phosgene with N,N'-organo-ureas; (RNH)(2)CO, (R = Me, Et, Pr and phenyl) also gave the corresponding [11C-carbonyl]isocyanates in moderate radiochemical yield (9-37%) from [11C]phosgene (decay corrected) in ca 16 min from EOB. For identification, the [11C-carbonyl]organo-isocyanates were derivatized with 1-(2-methoxyphenyl)piperazine in situ to [11C-carbonyl]carboxamides and the position of radiolabelling in the carbonyl group confirmed by [11/13C]co-labeling and subsequent carbon-13 NMR spectroscopy.

Carbon Radioisotopes↗

Worm burden and host responsiveness in Wuchereria bancrofti infection: use of antigen detection to refine earlier assessments from the South Pacific.

A population from the Wuchereria bancrofti-endemic island of Mauke was reevaluated retrospectively by use of the Og4C3 circulating antigen (CAg) enzyme-linked immunosorbent assay to assess active infection in relation to host responses by age and gender. Use of microfilaremia (Mf) alone misclassified approximately 50% of infected people, although CAg and Mf levels were positively correlated. Levels of CAg peaked between those aged 31-60 years; men aged > 60 years had a significantly higher CAg prevalence (> 90%) than women. Filaria-specific immunoglobulin (Ig) G4 reached maximum levels in both genders at age 51-60 years. By analysis of variance, both age and gender significantly influenced CAg and IgG4, with men having higher levels of both in the total population. Individuals positive for CAg had significantly lower lymphocyte proliferation responses to parasite antigen than did CAg-negative people, regardless of clinical status. This study reemphasizes the importance of CAg measurements for accurately assessing filarial prevalence and clinical status and demonstrates the relationship between active infection and immune responsiveness.

Adolescent↗

A rapid-format antibody card test for diagnosis of onchocerciasis.

Improved methods are needed for field diagnosis of onchocerciasis, to support efforts aimed at elimination of the disease. A rapid-format card test was evaluated that detects IgG4 antibodies to recombinant Onchocerca volvulus antigen Ov16 with serum samples from patients with onchocerciasis and with various types of control serum samples. The sensitivity of the test with serum samples from 106 microfilariae-positive subjects was 90.6%. The test was equally sensitive with serum samples obtained from patients in Africa and Latin America. Specificity was excellent; positive tests were observed for 2 of 38 serum samples from patients with other filarial infections and for 1 of 23 serum samples from patients with nonfilarial helminth infections. The 3 "false-positive" serum samples were from West Africans who could have been coinfected with onchocerciasis. No positive tests were observed with nonendemic serum samples from normal adults, patients with autoimmune disorders, or patients with the hyper-IgE syndrome. This new test holds great promise as a simple tool for diagnosis of onchocerciasis.

Adult↗

Helminth antigens selectively differentiate unsensitized CD45RA+ CD4+ human T cells in vitro.

Human filarial helminth infections are characterized by type 2 immune responses to parasite Ag that can persist for the life of the individual; one possible cause for this may be prenatal exposure to the blood-borne microfilarial (Mf) stage of the parasite. To examine the relationship between early exposure to filarial Ag and subsequent immune responsiveness, CD45RA+ CD4+ cells frp, normal unsensitized donors were stimulated in vitro with soluble microfilarial Ag (MfAg) from the filarial parasite Brugia malayi in the presence of APCs. MfAg alone induced proliferation and IFN-gamma and IL-5 production in unsensitized CD45RA+ CD4+ cells, demonstrating the ability of filarial Ags to prime naive T cells in the absence of exogenous cytokines and dendritic cells. Adding exogenous cytokine(s) (particularly IL-12 and IL-4) during priming was able to alter the MfAg-specific responses of CD45RA+ CD4+ cells as well as subsequent responses to Ag. Interestingly, priming solely with MfAg led to enhanced IL-5 production following Ag restimulation, suggesting that MfAg preferentially primes for type 2 responses. These data demonstrate that filarial Ags by themselves can specifically prime CD45RA+ CD4+ cells in vitro and do so in such a way as to deviate the immune response.

Animals↗

Oxford-Liverpool Inventory of Feelings and Experiences: reliability in an experimental population.

Further to the recent development of the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE), a short multidimensional schizotypy questionnaire, the present study set out to identify the reliability of all scales of this questionnaire within the same population. Participants were required to complete the O-LIFE on two separate occasions, whilst taking part in latent inhibition and negative priming experiments. All scales correlated highly, thus lending further support to the reliability of this time efficient questionnaire.

Adult↗

Evidence for protective immunity to bancroftian filariasis in the Cook Islands.

To challenge the concept of protective immunity in lymphatic filariasis, 19 adult residents of a Wuchereria bancrofti-endemic island who had been diagnosed 17 years earlier as putatively immune endemic normals (PI/EN) were reexamined. Even with continued exposure to infection, all 19 had maintained their apparent infection-free status. Studies to define the mechanisms underlying this putative immunity revealed that cellular immune responses (including proliferation; generation of interleukin [IL]-2, IL-5, IL-10, interferon-gamma, and granulocyte-macrophage colony-stimulating factor) to adult- and microfilarial-stage antigens, but not antibody responses, were markedly greater than those of 20 age-matched, infected patients. Furthermore, the PI/EN group was comprised of high- and low-responding persons who were clinically indistinguishable. These findings provide evidence that protective immunity to lymphatic filariasis does occur and that it is probably T cell-mediated.

Adolescent↗

Long-term effect of prenatal exposure to maternal microfilaraemia on immune responsiveness to filarial parasite antigens.

To identify long-term effects of prenatal exposure to maternal filarial-parasite infection, we assessed lymphocyte responses in 21 Polynesian children born 17-19 years previously to mothers diagnosed as being microfilaraemic or infection-free. All children lived on an island endemic for bancroftian filariasis but were free from infection at the time of study. While children (n = 10) of infection-free mothers responded vigorously to microfilarial antigen with lymphocyte proliferation, production of interleukin 2 (IL-2), IL-5, IL-10, granulocyte macrophage colony-stimulating factor (GM-CSF), and interferon gamma (IFN-gamma), cellular hyporesponsiveness was seen in children (n = 11) born to microfilaraemic mothers. The hyporesponsiveness appeared restricted to microfilarial antigens and did not extend to non-parasite antigens. These findings suggest that hyporesponsiveness resulted from in-utero acquisition of tolerance to microfilarial antigens in chronically-infected mothers.

Adolescent↗

Transient changes in cytokine profiles following ivermectin treatment of onchocerciasis.

Cytokine production by peripheral blood mononuclear cells after antigen or mitogen stimulation was assessed before and after semiannual ivermectin treatment of 27 patients with onchocerciasis. Before treatment, Onchocerca volvulus antigen (OvA) elicited interleukin (IL)-5 production but inhibited production of IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha. Six months after the first dose of ivermectin, there were increases in the IL-2, IL-4, IL-5, and interferon-gamma responses to mitogen and in the GM-CSF and IL-10 responses to OvA. By 24 months (after four ivermectin doses), OvA-induced GM-CSF production and mitogen-induced IL-2 and IL-10 production remained elevated above pretreatment levels, whereas that of other cytokines returned to or below pretreatment levels. These transient changes in cytokine response profiles of patients with onchocerciasis following ivermectin treatment likely reflect changes in antigen load.

Adult↗

Regulation of IL-5 in onchocerciasis. A critical role for IL-2.

The cytokine profiles of PBMC obtained from individuals "immune" to Onchocerca volvulus infection were compared to those from infected individuals. The immune individuals had significantly higher levels of both IL-2 and IL-5 in response to parasite Ag than did those individuals with active infection (mean IL-2 = 1.3 and 0.138 U/ml, respectively; mean IL-5 = 973 and 147.4 pg/ml, respectively), and there was a direct correlation between the production of IL-2 and IL-5. To examine the mechanism underlying the possible association between these two cytokines in patients infected with onchocerciasis, reverse transcription followed by polymerase chain reaction was used to measure IL-5 mRNA. In response to rIL-2, IL-5 mRNA appeared as early as early as 3 h after stimulation of patient PBMC, reaching a peak at 24 h; further, this response was inhibited with neutralizing antibodies to IL-2. IL-2 was unable to induce mRNA expression for IL-4, IFN-gamma, IL-10, or granulocyte-macrophage-CSF. To assess whether IL-2 was specifically responsible for the up-regulation of Ag-induced IL-5 production in patients with onchocerciasis, IL-5 mRNA expression was measured in PBMC stimulated with parasite Ag. Up-regulation of IL-5 mRNA was seen in all patients (peaking at 72 h) in response to Ag stimulation and was found to be independent of proliferation to Ag; in addition, this up-regulation was specifically inhibited by neutralizing anti-IL-2 antibodies. Further, the primary source of IL-5 mRNA was determined to be CD4+ T cells. These findings suggest that IL-2 production is required to induce IL-5 and further implicates IL-5 as a possible mediator of protection in onchocerciasis.

Animals↗

Immunity to onchocerciasis: recognition of larval antigens by humans putatively immune to Onchocerca volvulus infection.

Immunoblot analyses were done using sera from 12 individuals without evidence of onchocerciasis and 16 with active infection from an area of Guatemala holoendemic for onchocerciasis. For adult antigens from Onchocerca volvulus, no differences in antigen recognition could be identified between the two groups. In contrast, when infective larval (L3) antigen preparations derived from the related animal parasite Onchocerca lienalis were used, IgG from the "immune" individuals preferentially recognized a 45- to 50-kDa triplet and a 22-kDa L3 antigen. When L3 antigens of Brugia malayi were used, sera from putatively immune individuals identified a high-molecular-weight triplet/quadruplet plus several additional antigens of lower molecular weights that were recognized by sera from few (or none) of the infected patients. These findings define some differences in antibody specificity in onchocerciasis patients and therefore might define potential target antigens of humoral host defense. The exact nature of such defenses is unknown.

Adolescent↗

Immunologic responses to repeated ivermectin treatment in patients with onchocerciasis.

To assess the effect of ivermectin treatment on the immunologic status of individuals with onchocerciasis, 27 patients from Guatemala were studied before and at 6-month intervals during 2 years of repeated semiannual treatment with ivermectin. T cell proliferative responses to onchocercal antigen increased transiently by 6 months (mean stimulation index [SI] rising from 4.17 to 12.81) but returned to preivermectin levels thereafter. Changes in SI to nonparasite antigen paralleled those induced by parasite antigen. There were also significant decreases in levels of blood eosinophils, polyclonal IgG and IgE, parasite-specific IgG antibody, and IgG subclass antibodies by the end of the study. This study emphasizes the apparent long-term safety of ivermectin by demonstrating the absence of immunopathogenic responses induced by repeated ivermectin treatments.

Adolescent↗