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Biomedical subjects

C Jones

Publications and source records attributed to C Jones.

At least 109 records · Page 6Linked to original sources

Analysis of fumonisin B1-induced apoptosis.

Fumonisins are mycotoxins produced by Fusarium moniliforme, a prevalent fungus that infects corn and other cereal grains. Fumonisin B1(FB1 is the most common mycotoxin produced by F. moniliforme, suggesting it has toxicologic significance. The structure of FB1 resembles sphingoid bases, and it inhibits ceramide synthase. Because sphingoid bases regulate cell growth, differentiation, transformation, and apoptosis, it is not surprising to find that FB1 can alter growth of certain mammalian cells. Previous studies concluded FB1-induced apoptosis, or cell cycle arrest, in African green monkey kidney fibroblasts (CV-1). In this study we have identified genes that inhibit FB1 induced apoptosis in CV-1 cells and two mouse embryo fibroblasts (MEF). A baculovirus gene, inhibitor of apoptosis (CpIAP), protected these cells from apoptosis. CpIAP blocks apoptosis induced by the tumor necrosis factor (TNF) pathway as well as other mechanisms. Further support for the involvement of the TNF signal transduction pathway in FB1 induced apoptosis was the cleavage of caspase 8. Inhibition of caspases by the baculovirus gene (italic)p35 also inhibited FB1-induced apoptosis. The tumor suppressor gene p53 was not required for FB1 induced apoptosis because p53-/- MEF undergo apoptosis following FB1 treatment. Furthermore, Bcl-2 was not an effective inhibitor of FB1-induced apoptosis in CV-1 cells or p53+/+ MEF. In summary, these results provide new information to help understand the mechanism by which FB1 induces apoptosis.

Animals↗

Nonoperative management of blunt splenic and hepatic trauma in the pediatric population: significant differences between adult and pediatric surgeons?

Although operative management was the preferred method of treating blunt abdominal trauma in the past, recent literature and practice recommend a nonsurgical approach to most pediatric splenic and hepatic injuries. The majority of data supporting the safety and efficacy of this nonoperative approach are derived from university trauma programs with a pediatric center where care was managed by pediatric surgeons only. To evaluate the applicability of this approach in a regional trauma center where pediatric patients are managed by pediatric and non-pediatric surgeons we reviewed the experience at a Level II community trauma center. Fifty-four children (16 years of age or less) were admitted between April 1992 and April 1998 after sustaining blunt traumatic splenic and/or hepatic injuries. There were 37 (69%) males and 17 (31%) females; the average age was 11 years (range 4 months to 16 years). Of the 54 patients 34 (63%) sustained splenic injuries, 17 (31%) sustained hepatic injuries, and three (6%) sustained both splenic and hepatic injuries. All of these injuries were diagnosed by CT scan or during laparotomy. The average Injury Severity Score was 14.9 with a range from four to 57. Of the 47 patients initially admitted for nonoperative management one patient failed nonoperative management and required operative intervention. In our study 98 per cent (46 of 47 patients) of pediatric patients were successfully managed nonoperatively. Complications of nonoperative management occurred in two patients. Both developed splenic pseudocysts after splenic injury, which required later operative repair. These data are comparable with those from university trauma programs and confirm that nonoperative management is safe in a community trauma center. The majority of children with blunt splenic and hepatic trauma can be successfully treated without surgery, in a regional trauma center treated by nonpediatric trauma surgeons, if the decision is based on careful initial evaluation, aggressive resuscitation, and close observation of their hemodynamic stability.

Adult↗

Building capacity for awareness and risk factor identification in the community: the blood pressure assessment program of the Calgary Fire Department.

In 1995, the Calgary Fire Department developed a program to assess blood pressure in community fire stations, selected businesses and public venues. The program has gradually expanded. Currently, all 30 fire stations across Calgary, Alberta assess blood pressures for the public seven days per week throughout the year. Since 1995, there have been 10,883 measurements in 3477 people. Most people (2106) assessed had hypertensive readings, and 72 had readings greater than 220 mmHg systolic or greater than 120 mmHg diastolic, and were referred for immediate medical assessment. The program has been recently integrated into a more global vision for the prevention and control of cardiovascular disease in Calgary. Future plans include offering lipid assessments, assisting other communities to adopt the program and using the program to provide physical measures (of blood pressure, glucose, total and high density lipoprotein cholesterol, height and weight) to an ongoing questionnaire that surveys the health of Calgarians. The history of the program, its training methods, quality control, preliminary results and future plans are presented in detail to provide an example of a community-based program that could aid in the detection, monitoring and awareness of hypertension.

Adult↗

The problem of erectile dysfunction following myocardial infarction.

The causes of erection problems after an MI can be physical, psychological, a result of medication or a combination of these factors. This paper examines the causes and considers ways in which nurses can help men experiencing this problem, who may still feel embarrassed to broach this subject even though it is now more publically discussed.

Erectile Dysfunction↗

Complementary therapies: what is the evidence for their use?

Complementary therapies are being increasingly used by patients and health-care professionals, but often with little awareness of the evidence for their use. The Internet offers a valuable and easy-to-use resource for assessing a growing amount of published information. Nurses need to be aware of a treatment's effectiveness and warn patients of potential risks or unprofessional claims.

Complementary Therapies↗

NMR assignments for glucosylated and galactosylated N-acetylhexosaminitols: oligosaccharide alditols related to O-linked glycans from the protozoan parasite Trypanosoma cruzi.

We report full 1H and 13C NMR assignments for 13 gluco- or galacto-pyranosylated derivatives of GlcNAc-ol, GalNAc-ol or ManNAc-ol, many of which have been prepared by enzymatic methods. These spectra are reference data to aid the structural analysis by NMR spectroscopy of glycosylated alditols derived from the mucin of the protozoan parasite Trypanosoma cruzi. A series of structural reporter groups for the derivatives from this unusual series of O-glycans are described.

Animals↗

The effect of a monoclonal antibody coupled to ricin A chain-derived peptides on endothelial cells in vitro: insights into toxin-mediated vascular damage.

Immunotoxins (ITs) containing plant or bacterial toxins have a dose-limiting toxicity of vascular leak syndrome (VLS) in humans. The active A chain of ricin toxin (RTA), other toxins, ribosome-inactivating proteins, and the VLS-inducing cytokine IL-2 contain the conserved sequence motif (x)D(y) where x = L, I, G, or V and y = V, L, or S. RTA-derived LDV-containing peptides attached to a monoclonal antibody, RFB4, induce endothelial cell (EC) damage in vitro and vascular leak in two animal models in vivo. We have now investigated the mechanism(s) by which this occurs and have found that (1) the exposed D75 in the LDV sequence in RTA and the C-terminal flanking threonine play critical roles in the ability of RFB4-conjugated RTA peptide to bind to and damage ECs and (2) the LDV sequence in RTA induces early manifestations of apoptosis in HUVECs by activating caspase-3. These data suggest that RTA-mediated inhibition of protein synthesis (due to its active site) and apoptosis (due to LDV) may be mediated by different portions of the RTA molecule. These results suggest that ITs prepared with RTA mutants containing alterations in LDVT may kill tumor cells in vivo in the absence of EC-mediated VLS.

Amino Acid Motifs↗

Siglec-9, a novel sialic acid binding member of the immunoglobulin superfamily expressed broadly on human blood leukocytes.

Here we characterize the properties and expression pattern of Siglec-9 (sialic acid-binding Ig-like lectin-9), a new member of the Siglec subgroup of the immunoglobulin superfamily. A full-length cDNA encoding Siglec-9 was isolated from a dibutyryl cAMP-treated HL-60 cell cDNA library. Siglec-9 is predicted to contain three extracellular immunoglobulin-like domains that comprise an N-terminal V-set domain and two C2-set domains, a transmembrane region and a cytoplasmic tail containing two putative tyrosine-based signaling motifs. Overall, Siglec-9 is approximately 80% identical in amino acid sequence to Siglec-7, suggesting that the genes encoding these two proteins arose relatively recently by gene duplication. Binding assays showed that, similar to Siglec-7, Siglec-9 recognized sialic acid in either the alpha2,3- or alpha2, 6-glycosidic linkage to galactose. Using a specific mAb, Siglec-9 was found to be expressed at high or intermediate levels by monocytes, neutrophils, and a minor population of CD16(+), CD56(-) cells. Weaker expression was observed on approximately 50% of B cells and NK cells and minor subsets of CD8(+) T cells and CD4(+) T cells. These results show that despite their high degree of sequence similarity, Siglec-7 and Siglec-9 have distinct expression profiles.

Amino Acid Sequence↗

Analysis of latency in cattle after inoculation with a temperature sensitive mutant of bovine herpesvirus 1 (RLB106).

Calves were inoculated with the bovine herpes virus 1 (BHV-1) vaccine strain (RLB 106), which is a temperature sensitive mutant. The route of inoculation was intranasal instillation or intramuscular (i.m.) injection (flank or neck). As a control, five calves were given placebo by i.m. injection of the neck. Regardless of the infection route, clinical symptoms did not occur. However, BHV-1 neutralizing antibodies were detected after inoculation demonstrating that sero-conversion occurred. At 60 days post-inoculation, dexamethasone was given by i.m. injection to attempt reactivation of RLB 106. Only those calves inoculated by the intranasal route shed virus leading to an increase in BHV-1 specific antibodies. As expected, viral DNA and the latency related-RNA were detected in trigeminal ganglia (TG) of calves inoculated by the intranasal route. In contrast, viral nucleic acid was not detected in TG of calves inoculated by the i.m. route or in calves inoculated with placebo. In cervical ganglia or sacral dorsal root ganglia, viral nucleic acid was not consistently detected. This study provides evidence that efficient latency and reactivation does not occur following i.m. inoculation. Since serum-neutralizing antibodies were detected in all inoculated calves, i.m. inoculation led to sero-conversion.

Administration, Intranasal↗

Regulation of bradykinin receptor gene expression in human lung fibroblasts.

In WI-38 human fibroblasts, interleukin-1 beta and tumour necrosis factor-alpha (TNF-alpha) increased bradykinin B(1) receptor mRNA, which peaked between 2 and 4 h, remaining elevated for 20 h. Binding of the bradykinin B(1) receptor selective ligand [3H]des-Arg(10)-kallidin, also increased, peaking at 4 h and remaining elevated for 20 h. The B(max) value for [3H]des-Arg(10)-kallidin rose from 280+/-102 fmol/mg (n=3) to 701+/-147 fmol/mg (n=3), but the K(D) value remained unaltered (control, 1.04+/-0.33 nM (n=3); interleukin-1 beta, 0.88+/-0.41 nM (n=3)). The interleukin-1 beta-induced [3H]des-Arg(10)-kallidin binding sites were functional receptors, as bradykinin B(1) receptor agonist-induced responses increased in treated cells. Bradykinin B(2) receptor mRNA and [3H]bradykinin binding were upregulated by interleukin-1 beta, but not TNF-alpha. The effect of interleukin-1 beta on bradykinin B(2) receptors was smaller than for bradykinin B(1) receptors. Cycloheximide prevented interleukin-1 beta-mediated increases in B(1) and B(2) binding, but not mRNA suggesting that de novo synthesis of a transcriptional activator was unnecessary.

Binding, Competitive↗

Cloning and chromosomal localization of the human BARX2 homeobox protein gene.

The human BARX2 gene encodes a homeodomain-containing protein of 254 amino acids, which binds optimally to the DNA consensus sequence YYTAATGRTTTTY. BARX2 is highly expressed in adult salivary gland and is expressed at lower levels in other tissues, including mammary gland, kidney, and placenta. The BARX2 gene consists of four exons, and is located on human chromosome 11q25. This chromosomal location is within the minimal deletion region for Jacobsen syndrome, a syndrome including craniosynostosis and other developmental abnormalities. This chromosomal location, along with the reported expression of murine barx2 in craniofacial development, suggests that BARX2 may be causally involved in the craniofacial abnormalities in Jacobsen syndrome.

Amino Acid Sequence↗

Chandra X-Ray Observations of the Hydra A Cluster: An Interaction between the Radio Source and the X-Ray-emitting Gas.

We present Chandra X-ray observations of the Hydra A cluster of galaxies, and we report the discovery of structure in the central 80 kpc of the cluster's X-ray-emitting gas. The most remarkable structures are depressions in the X-ray surface brightness, approximately 25-35 kpc in diameter, that are coincident with Hydra A's radio lobes. The depressions are nearly devoid of X-ray-emitting gas, and there is no evidence for shock-heated gas surrounding the radio lobes. We suggest that the gas within the surface brightness depressions was displaced as the radio lobes expanded subsonically, leaving cavities in the hot atmosphere. The gas temperature declines from 4 keV at 70 kpc to 3 keV in the inner 20 kpc of the brightest cluster galaxy (BCG), and the cooling time of the gas is approximately 600 Myr in the inner 10 kpc. These properties are consistent with the presence of an approximately 34 M middle dot in circle yr-1 cooling flow within a 70 kpc radius. Bright X-ray emission is present in the BCG surrounding a recently accreted disk of nebular emission and young stars. The star formation rate is commensurate with the cooling rate of the hot gas within the volume of the disk, although the sink for the material that may be cooling at larger radii remains elusive. A bright, unresolved X-ray source is present in the BCG's nucleus, coincident with the radio core. Its X-ray spectrum is consistent with a power law absorbed by a foreground NH approximately 4x1022 cm-2 column of hydrogen. This column is roughly consistent with the hydrogen column seen in absorption toward the less, similar24 pc diameter VLBA radio source. Apart from the point source, no evidence for excess X-ray absorption above the Galactic column is found.

Journal Article↗

Co-localisation of CCG repeats and chromosome deletion breakpoints in Jacobsen syndrome: evidence for a common mechanism of chromosome breakage.

Folate-sensitive fragile sites are associated with the expansion and hypermethylation of CCG-repeats. The fragile site in 11q23.3, FRA11B, has been shown to cause chromosome deletions in vivo, its expression being associated with Jacobsen (11q-) syndrome. However, the majority of Jacobsen deletions are distal to FRA11B and are not related to its expression. To test the hypothesis that other unidentified fragile sites might be located in 11q23.3-24 and may cause these deletions, we have identified and characterised CCG-trinucleotide repeats within a 40 Mb YAC contig spanning distal chromosome 11q. Only eight CCG-repeats were identified within the entire YAC contig (not including FRA11B ), six of which map to the region of 11q23.3-24 that includes Jacobsen deletions. We have previously collated the deletion mapping data of 24 Jacobsen patients with the physical map of chromosome 11q, and accurately localised six breakpoints to short intervals corresponding to individual YAC clones. We now show that in each of these cases, YAC clones found to contain a deletion breakpoint also contain a CCG-repeat. The improved analysis of one of these deletions, together with those of several new Jacobsen cases, further strengthens this association by localising five breakpoints to individual PAC clones containing CCG-repeats. These data provide strong evidence for the non-random clustering of chromosome deletion breakpoints with CCG-repeats, and suggests that they may play an important role in a common mechanism of chromosome breakage.

Abnormalities, Multiple↗

Full assignment of the proton and carbon NMR spectra and revised structure for the capsular polysaccharide from Streptococcus pneumoniae type 17F.

Full proton, 13C and 31P NMR assignments for the capsular polysaccharide from Streptococcus pneumoniae Type 17F are reported, and a revised structure differing in the anomeric configuration of the sidechain beta-Galp residue proposed. This polysaccharide is a component of the current 23-valent polysaccharide vaccine. The implications of this revised structure for published work are discussed.

Carbohydrate Sequence↗