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Biomedical subjects

C Jones

Publications and source records attributed to C Jones.

At least 91 records · Page 5Linked to original sources
PubMed2001

Effects of genotypically different strains of Helicobacter pylori on human microvascular endothelial cells in vitro.

Helicobacter pylori induces a number of disturbances in rodent gastric microcirculation in vivo. These events may result from direct necrotic or apoptotic damage to endothelial cells. This study therefore aimed to investigate the effects of genotypically different H. pylori strains on microvascular endothelial cell (MVEC) viability in vitro. Four H. pylori extracts were prepared from strains with different cagA or vacA status. MVECs were plated into 96-well plates and coincubated with 50 microl of extract or vehicle for 24, 48, 72, or 96 hr. An MPP assay quantified overall MVEC viability. The dual labeling of MVECs with propidium iodide and Hoechst 33342 distinguished between necrotic and apoptotic cell death, respectively, and allowed total number of viable cells to be determined. All strains of H. pylori decreased cell viability after 72 and 96 hr. Neither necrosis or apoptosis was observed. Counting total number of viable cells revealed decreased cell proliferation with all strains when compared to controls, again reaching significance at 72 and 96 hr. In conclusion, both the MTT assay and the diret cell counting technique demonstrated that all H. pylori strains induced cytostatic but not cytotoxic effects on MVECs. This suggests that microcirculatory disturbances observed in vivo may not be the result of direct endothelial cell damage. However, inhibition of angiogenesis may explain why ulcer healing is delayed in H. pylori-infected patients.

Apoptosis↗
PubMed2001

Molecular characterization of a myelodysplasia-associated chromosome 7 inversion.

Chromosome 7 abnormalities are observed in a wide range of myeloid disorders, particularly myelodysplasia (MDS) and acute myeloid leukaemia (AML). Monosomy 7 and 7q deletions are the most frequent abnormalities, although translocations and inversions involving 7q also occur. The region 7q22--q34 may contain as many as four distinct minimal regions of deletion (MDRs), which are thought to contain one or more myeloid tumour-suppressor genes. We have defined previously the proximal breakpoint of a constitutional 7q22--q34 inversion, carried in a cell line derived from a member of a family with a history of MDS. A YAC clone spanning this breakpoint was identified. Both inversion breakpoints have now been cloned and sequenced, placing the proximal breakpoint 40 kb centromeric to the TAC2 (tachykinin 2) gene and the distal breakpoint 42 kb telomeric to the SSBP (mitochondrial single-stranded DNA-binding protein) gene. Sequence alignments revealed small (3--4 bp) duplications at the inversion breakpoints, suggesting that the mechanism of inversion involved the creation of staggered breaks and filling in of the overhanging ends. A 190-bp Alu--Alu deletion close to the distal breakpoint was also detected and may have contributed to the inversion.

Autoradiography↗
PubMed2001

Structure of an acidic exopolysaccharide produced by the diazotrophic endophytic bacterium Burkholderia brasiliensis.

The structure of an exopolysaccharide (EPS) produced by Burkholderia brasiliensis, a diazotrophic endophytic organism originally isolated from rice roots, has been determined. The bacterium was grown in a synthetic medium, containing mannitol and glutamate, which favours the expression of two anionic EPSs, which were separated by anion-exchange chromatography. The structure of the repeat unit of EPS A, eluted at higher ionic strength, was determined by a combination of methylation analysis, partial hydrolysis, chemical degradations, and NMR spectroscopic studies, and shown to be the linear O-acetylated pentasaccharide: -->4)-alpha-D-Glcp-(1-->2)-alpha-L-Rhap-(1-->4)-alpha-D-GlcpA-(1-->3)-beta-L-Rhap[2OAc]-(1-->4)-beta-D-Glcp-(1-->.

Burkholderia↗
PubMed2001

Characterization of novel structures of mannosylinositolphosphorylceramides from the yeast forms of Sporothrix schenckii.

Novel structures of glycoinositolphosphorylceramide (GIPC) from the infective yeast form of Sporothrix schenckii were determined by methylation analysis, mass spectrometry and NMR spectroscopy. The lipid portion was characterized as a ceramide composed of C-18 phytosphingosine N-acylated by either 2-hydroxylignoceric acid (80%), lignoceric (15%) or 2,3-dihydroxylignoceric acids (5%). The ceramide was linked through a phosphodiester to myo-inositol (Ins) which is substituted on position O-6 by an oligomannose chain. GIPC-derived Ins oligomannosides were liberated by ammonolysis and characterized as: Manpalpha1-->6Ins; Manpalpha1-->3Manpalpha1-->6Ins; Manpalpha1-->6Manpalpha1-->3Manpalpha1-->3Manpalpha1-->6Ins; Manpalpha1-->2Manpalpha1-->6Manpalpha1-->3Manpalpha1-->3Manpalpha1-->6Ins. These structures comprise a novel family of fungal GIPC, as they contain the Manpalpha1-->6Ins substructure, which has not previously been characterized unambigously, and may be acylated with a 2,3 dihydroxylignoceric fatty acid, a feature hitherto undescribed in fungal lipids.

Carbohydrate Sequence↗
PubMed2001

Mortality risk by hemodialyzer reuse practice and dialyzer membrane characteristics: results from the usrds dialysis morbidity and mortality study.

Hemodialyzer reuse is commonly practiced in the United States. Recent studies have raised concerns about the mortality risk associated with certain reuse practices. We evaluated adjusted mortality risk during 1- to 2-year follow-up in a representative sample of 12,791 chronic hemodialysis patients treated in 1,394 dialysis facilities from 1994 through 1995. Medical record abstraction provided data on reuse practice, use of bleach, dialyzer membrane, dialysis dose, and patient characteristics and comorbidity. Mortality risk was analyzed by bootstrapped Cox models by (1) no reuse versus reuse, (2) reuse agent, and (3) dialyzer membrane with and without the use of bleach, while considering dialysis and patient factors. The relative risk (RR) for mortality did not differ for patients in reuse versus no-reuse units (RR = 0.96; 95% confidence interval [CI], 0.86 to 1.08; P > 0.50), and similar results were found with different levels of adjustment and subgroups (RR = 1.01 to 1.05; 95% CI, lower bound > 0.90, upper bound < 1.19 each; each P > 0.40). The RR for peracetic acid mixture versus formalin varied significantly by membrane type and use of bleach during reprocessing, achieving borderline significance for synthetic membranes. Among synthetic membranes, mortality was greater with low-flux than high-flux membranes (RR = 1.24; 95% CI, 1.02 to 1.52; P = 0.04) and without than with bleach during reprocessing (RR = 1.24; 95% CI, 1.01 to 1.48; P = 0.04). Among all membranes, mortality was lowest for patients treated with high-flux synthetic membranes (RR = 0.82; 95% CI, 0.72 to 0.93; P = 0.002). Although mortality was not greater in reuse than no-reuse units overall, differences may exist in mortality risk by reuse agent. Use of high-flux synthetic membrane dialyzers was associated with lower mortality risk, particularly when exposed to bleach. Clearance of larger molecules may have a role.

Ambulatory Care Facilities↗
PubMed2001

A comparison of the clinical, histopathologic, and ultrastructural phenotypes in carriers of X-linked and autosomal recessive Alport's syndrome.

Previous series that described phenotypes in carriers of Alport's syndrome did not distinguish genetically between carriers of X-linked and autosomal recessive disease. In this study, modes of inheritance in unselected families with Alport's syndrome associated with two city and two provincial hospitals were determined using microsatellite markers, and carriers of disease haplotypes were identified within these families. All 47 carriers (100%) from 18 families with X-linked Alport's syndrome had dysmorphic hematuria on phase-contrast microscopy, but few developed renal failure (3 of 40 carriers; 8%), clinical hearing loss (2 of 45 carriers; 4%), retinopathy (1 of 30 carriers; 3%), or lenticonus (0 of 30 carriers; 0%). Eleven of the 14 carriers (79%) from 2 families with autosomal recessive disease had dysmorphic hematuria, but none had renal failure, clinical hearing loss, retinopathy, or lenticonus. Urinary red blood cell counts in carriers of X-linked Alport's syndrome were greater than those in carriers of autosomal recessive disease (P < 0.0001), but the frequency of proteinuria and hypertension and levels of proteinuria were not different. There was more tubulointerstitial damage in carriers of X-linked disease (P = 0.012); however, carriers of autosomal recessive disease had more widespread and more uniform thinning of the glomerular basement membrane (P < 0.0001) and less lamellation (P < 0.04).

Adolescent↗
PubMed2001

Partnering for injury prevention: evaluation of a curriculum-based intervention program among elementary school children.

A randomized pretest and posttest comparative design was used to evaluate the outcome of implementing Think First for Kids (TFFK), an injury prevention program for children grades 1, 2, and 3, among intervention and controls schools. The study showed that children often lack basic knowledge regarding safety and do not recognize behaviors considered high risk for injury. By using multivariate analysis, the intervention children had a significantly greater increase in knowledge about the brain and spinal cord and safe behaviors to prevent traumatic injury, and a decrease in self-reported, high-risk behaviors (p < .001) when compared with control subjects, adjusting for the covariates gender, socioeconomic status, and race/ethnicity. African American and Hispanic children, although displaying the lowest test scores at baseline, had the largest absolute improvement in posttest scores. The TFKK prevention program addresses the leading causes of trauma among children including sports, motor vehicle crashes, falls, drowning, and pedestrian injuries.

Accident Prevention↗
PubMed2001

Suspicious death related to gamma-hydroxybutyrate (GHB) toxicity.

I present a case report of a death following the use of gamma-hydroxybutyrate (GHB) in combination with alcohol; this was the third death reported in the UK, with, to date, at least 27 deaths in America. GHB is also known as one of those used in drug rape; in particular, as it is colourless and odourless, it is very easy to add to drinks; although it has a short half-life of 20 min, the effect is prolonged with the alcohol used to disguise it and it has a marked amnesic effect, making it harder for the victim to present for help and forensic investigation. There is currently a campaign to consider re-classification of gamma-hydroxybutyrate as a Schedule1 drug, whereby possession will become a criminal offence.

Journal Article↗
PubMed2001

Sociodrama: a teaching method for expanding the understanding of clinical issues.

Sociodrama is a powerful teaching strategy that combines a case study approach with traditional role-play methodology to illustrate critical issues in end-of-life care. Building on principles of adult learning and communication skills, the sociodrama method enables the skilled facilitator to draw on the learner's past experiences as resources for teaching and reflective practice. This article describes the use of sociodrama in end-of-life education with illustrations from actual sessions including key discussion points, a typical instructional plan and staging tips.

Attitude of Health Personnel↗
PubMed2001

Structure of O-glycosidically linked oligosaccharides from glycoproteins of Trypanosoma cruzi CL-Brener strain: evidence for the presence of O-linked sialyl-oligosaccharides.

Glycoproteins on the cell surface of Trypanosoma cruzi are known to play important roles in the interaction of the parasite with the host cells. We previously determined the structures of the O-glycan chains from the sialoglycoproteins (mucin-like molecules) of the G- and Y-strains and observed significant differences between them. We now report the structures of the sialylated and nonsialylated O-linked oligosaccharides isolated from the cell surface glycoproteins of the myotropic CL-Brener strain grown in the presence of fetal calf serum. The structures of the O-linked oligosaccharide alditols obtained by reductive beta-elimination of the sialoglycoprotein were determined by a combination of methylation analysis, fast atom bombardment-mass spectrometry and nuclear magnetic resonance spectroscopy. The presence of a beta-galactopyranose substituent on the N-acetylglucosamine O-4 position shows that these O-linked oligosaccharides from CL-Brener strain belong to the same family as those isolated from mucins expressed by T. cruzi Y strain, a reticulotropic strain. In addition, novel O-glycans, including alpha2-3 mono-sialylated species are described.

Animals↗
PubMed2001

Memory, delusions, and the development of acute posttraumatic stress disorder-related symptoms after intensive care.

OBJECTIVE: To examine prospectively the relationship between memories of intensive care (ICU) and levels of anxiety after ICU discharge, the stability of these memories with time, and their relationship to the development of acute posttraumatic stress disorder (PTSD)-related symptoms. DESIGN: Case series cohort assessed by interview at 2 and 8 wks after ICU discharge. SETTING: District general hospital (serving a population of 350,000) general intensive care unit. PATIENTS: Memories of ICU and anxiety levels were studied in 45 patients after ICU discharge. Thirty patients were examined again at 8 wks to assess memory stability and development of acute PTSD-related symptoms. MEASUREMENTS AND MAIN RESULTS: Standardized interviews and questionnaires were used to assess memory for ICU, anxiety, and depression 2 wks after ICU discharge. In addition, PTSD-related symptoms and panic were assessed 8 wks after ICU discharge. A total of 33 of 45 patients had delusional memories from ICU at 2 wks; nine of the patients with delusional memories had no factual memories, and these patients had higher anxiety levels 2 wks after ICU discharge (p < .0001). Thirty patients had paired assessments at 2 and 8 wks. Those patients who had no factual recall of ICU but had delusional memories at 2 wks scored highly for PTSD-related symptoms and panic attacks at 8 wks (p = .023 and .014, respectively). The only predictors of possible acute PTSD-related symptoms at the 8-wk assessment were trait anxiety (p = .006) and having delusional memories without recall of factual events in the ICU at 2 wks (p < .0001). Only delusional memories were retained over time, whereas the recall of factual events in the ICU declined. CONCLUSIONS: We propose that the development of acute PTSD-related symptoms may be related more to recall of delusions alone. This study suggests that even relatively unpleasant memories for real events during critical illness may give some protection from anxiety and the later development of PTSD-related symptoms when memories of delusions are prominent.

Acute Disease↗
PubMed2001

A mutation in the latency-related gene of bovine herpesvirus 1 leads to impaired ocular shedding in acutely infected calves.

Bovine herpesvirus 1 (BHV-1) is an important pathogen of cattle, and infection is usually initiated in the ocular or nasal cavity. Like other alphaherpesviruses, BHV-1 establishes latency in sensory neurons but has the potential of reactivating from latency and spreading. The only abundant viral transcript expressed during latency is the latency-related (LR) RNA, which is alternatively spliced in trigeminal ganglia during acute infection (L. R. Devireddy and C. Jones, J. Virol. 72:7294-7301, 1998). LR gene products inhibit cell cycle progression (Y. Jiang, A. Hossain, M. T. Winkler, T. Holt, A. Doster, and C. Jones, J. Virol. 72:8133-8142, 1998) and chemically induced apoptosis (J. Ciacci-Zannela, M. Stone, G. Henderson, and C. Jones. J. Virol. 73:9734-9740, 1999). Although these studies suggest that LR gene products play an important role in the latency/pathogenesis of BHV-1, construction of a mutant is necessary to test this hypothesis. Because the bICP0 gene overlaps and is antisense to the LR gene, it was necessary to mutate the LR gene without altering bICP0 expression. This was accomplished by inserting three stop codons near the beginning of the LR RNA, thus interfering with expression of proteins expressed by the LR RNA. The LR mutant virus grew with wild-type (WT) efficiency in bovine kidney (MDBK) cells and expressed bICP0 at least as efficiently as WT BHV-1 or the LR rescued virus. When calves were infected with the LR mutant, we observed a dramatic decrease (3 to 4 log units) in ocular shedding during acute infection relative to WT or the LR rescued virus. In contrast, shedding of the LR mutant from the nasal cavity was not significantly different from that of the WT or the LR rescued virus. Calves infected with the LR mutant exhibited mild clinical symptoms, but they seroconverted. Neutralizing antibody titers were lower in calves infected with the LR mutant, confirming reduced growth. In summary, this study suggests that an LR protein promotes ocular shedding during acute infection of calves.

Animals↗
PubMed2001

The bovine herpesvirus 1 immediate-early protein (bICP0) associates with histone deacetylase 1 to activate transcription.

Infected-cell protein 0 encoded by bovine herpesvirus 1 (BHV-1) (bICP0) is necessary for efficient productive infection, in large part, because it activates all 3 classes of BHV-1 genes (U. V. Wirth, C. Fraefel, B. Vogt, C. Vlcek, V. Paces, and M. Schwyzer, J. Virol. 66:2763-2772, 1992). Although bICP0 is believed to be a functional homologue of herpes simplex virus type 1-encoded ICP0, the only well-conserved domain between the proteins is a zinc ring finger located near the amino terminus of both proteins. Our previous studies demonstrated that bICP0 is toxic to transfected cells but does not appear to directly induce apoptosis (Inman, M., Y. Zhang, V. Geiser, and C. Jones, J. Gen. Virol. 82:483-492, 2001). C-terminal sequences in the last 320 amino acids of bICP0 mediate subcellular localization. Mutagenesis of the zinc ring finger within bICP0 revealed that this domain was important for transcriptional activation. In this study, we demonstrate that bICP0 interacts with histone deacetylase 1 (HDAC1), which results in activation of a simple promoter containing four consensus Myc-Max binding sites. The interaction between bICP0 and HDAC1 correlated with inhibition of Mad-dependent transcriptional repression. In resting CV-1 cells, bICP0 relieved HDAC1-mediated transcriptional repression. The zinc ring finger was required for relieving HDAC1-induced repression but not for interacting with HDAC1. In fetal bovine lung cells but not in a human epithelial cell line, bICP0 expression correlated with reduced steady-state levels of HDAC1 in crude cytoplasmic extracts. We hypothesize that the ability of bICP0 to overcome HDAC1-induced repression plays a role in promoting productive infection in highly differentiated cell types.

Amino Acid Sequence↗
PubMed2001

Region of herpes simplex virus type 1 latency-associated transcript sufficient for wild-type spontaneous reactivation promotes cell survival in tissue culture.

The latency-associated transcript (LAT) is the only abundant herpes simplex virus type 1 (HSV-1) transcript expressed during latency. In the rabbit eye model, LAT null mutants do not reactivate efficiently from latency. We recently demonstrated that the LAT null mutant dLAT2903 induces increased levels of apoptosis in trigeminal ganglia of infected rabbits compared to LAT+ strains (G.-C. Perng, C. Jones, J. Ciacci-Zarella, M. Stone, G. Henderson, A. Yokht, S. M. Slanina, F. M. Hoffman, H. Ghiasi, A. B. Nesburn, and C. S. Wechsler, Science 287:1500-1503, 2000). The same study also demonstrated that a plasmid expressing LAT nucleotides 301 to 2659 enhanced cell survival of transfected cells after induction of apoptosis. Consequently, we hypothesized that LAT enhances spontaneous reactivation in part, because it promotes survival of infected neurons. Here we report on the ability of plasmids expressing different portions of the 5' end of LAT to promote cell survival after induction of apoptosis. A plasmid expressing the first 1.5 kb of LAT (LAT nucleotides 1 to 1499) promoted cell survival in neuro-2A (mouse neuronal) and CV-1 (monkey fibroblast) cells. A plasmid expressing just the first 811 nucleotides of LAT promoted cell survival less efficiently. Plasmids expressing the first 661 nucleotides or less of LAT did not promote cell survival. We previously showed that a mutant expressing just the first 1.5 kb of LAT has wild-type spontaneous reactivation in rabbits, and a mutant expressing just the first 811 nucleotides of LAT has a reactivation frequency higher than that of dLAT2903 but lower than that of wild-type virus. In addition, mutants reported here for the first time, expressing just the first 661 or 76 nucleotides of LAT, had spontaneous reactivation indistinguishable from that of the LAT null mutant dLAT2903. In summary, these studies provide evidence that there is a functional relationship between the ability of LAT to promote cell survival and its ability to enhance spontaneous reactivation.

Animals↗
PubMed2001

Cdc5 interacts with the Wee1 kinase in budding yeast.

Development of a multicellular organism requires that mitosis and morphogenesis be coordinated. These processes must also be synchronized during the growth of unicellular organisms. In the yeast Saccharomyces cerevisiae, mitosis is dependent on the prior growth of a daughter cell in the form of a bud. Overexpression of wild-type Polo-like kinase Cdc5 or a catalytically inactive form resulted in the formation of multinucleate cells in budding yeast. Immunofluorescence analysis of these multinulceate cells showed that mitosis and bud formation were no longer linked. Others have shown that Swe1 is required for coupling mitosis to bud formation during a perturbed cell cycle. When the normal pathway of bud formation is perturbed, Swe1 functions to delay mitosis through negative regulation of Clb/Cdk. In cells lacking Swe1, multinucleate cells are formed in response to delays in bud formation. Affinity purification, two-hybrid analysis, and mutant characterization results suggested that Cdc5 and Swe1 interact. From these results, we conclude that multinucleate formation in response to Cdc5 overexpression is linked to titration of Swe1 function. These results also suggest that Cdc5 may be a negative regulator of Swe1.

Cell Cycle Proteins↗
PubMed2001

Loss of heterozygosity at cylindromatosis gene locus, CYLD, in sporadic skin adnexal tumours.

AIM: The gene for familial cylindromatosis (CYLD) has been localised to chromosome 16q, and has recently been cloned. Loss of heterozygosity (LOH) at 16q has also been demonstrated in sporadic cylindromas. The aim of this study was to investigate whether CYLD plays a role in the development of other skin appendage tumours. METHODS: A total of 55 cases of skin adnexal tumours, comprising 12 different types, and a control group of 14 squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs) were studied. Three microsatellites (D16S407 (16p), D16S304 (16q), and D16S308 (16q)) were analysed for LOH after microdissection from paraffin wax embedded sections using laser capture microdissection. RESULTS: In keeping with previous data, a proportion of cylindromas exhibited LOH at markers on 16q, but not at 16p. The skin adnexal tumours showing a similar pattern included apocrine hydrocystomas, eccrine spiradenomas, and sebaceous adenoma. One case of syringoma showed LOH at 16q, and a further case at 16p, but not 16q. One case of eccrine hydrocystoma showed loss at 16p, but not 16q. The remaining tumours were either negative or non-informative. All tumours in the control group were either negative or non-informative, except for a single case of BCC showing LOH at 16q. CONCLUSION: CYLD may be involved in the development of skin adnexal tumours other than cylindromas.

Adenoma↗
PubMed2001

McCune-Albright syndrome: growth hormone dynamics in pregnancy.

Excess GH secretion has a well recognized association with McCune-Albright syndrome. Although there have been a number of reported pregnancies in uncontrolled acromegaly, none has been described in the McCune-Albright syndrome. We have studied the GH and insulin-like growth factor I (IGF-I) profiles in a patient with confirmed McCune-Albright syndrome and GH hypersecretion throughout a successful pregnancy and postpartum period. Prepregnancy, IGF-I was 60.6 nmol/L (normal, 18.0--43.1), and the daytime GH profile measured using assay A was 9.6--14.0 mU/L. At 13 weeks gestation there was a decline of IGF-I to 33.9 nmol/L and in the daytime GH profile (assay A) to 5.4--6.8 mU/L. At 24 weeks, IGF-I had risen to 51.6 nmol/L. A simultaneous daytime GH profile at this time using assay A revealed levels between 21.3--22.1 mU/L, but only 2.1--3.0 mU/L with assay B. Assay A has significant cross-reactivity with human placental lactogen (HPL), unlike assay B. At 36 weeks, IGF-I was still elevated at 56.6 nmol/L, with a daytime GH profile of 16.6--17.7 mU/L using assay A and 1.5--3.9 mU/L with assay B. At 12 weeks postpartum, IGF-I was 71.4 nmol/L, and the daytime GH profile with assay B was 5.6--8.6 mU/L. These data support a picture of GH suppression during pregnancy in acromegaly associated with McCune-Albright syndrome, shown best with assay B, which discriminates between GH and HPL. These results contrast with previous reports of pregnancy in uncontrolled acromegalics, in whom pituitary GH levels were unaffected by pregnancy, and total GH and IGF-I levels were noted to be elevated. These data suggest that GH secretion in a pregnant acromegalic with the McCune-Albright syndrome may not be entirely autonomous, as seen in classic acromegaly, but may be associated with a degree of negative feedback control that could be exerted by a circulating factor of placental origin, probably HPL or placental GH.

Adult↗