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Biomedical subjects

C Jones

Publications and source records attributed to C Jones.

At least 199 records · Page 11Linked to original sources

Cloning and expression of an immunoglobulin superfamily gene (IGSF1) in Xq25.

We have isolated a novel full-length cDNA for a gene (IGSF1) located in distal Xq25. This transcript is highly expressed in adult testis and fetal liver but is undetectable in adult liver. A smaller alternate form is highly expressed in adult heart. The gene encodes a protein of 1327 amino acids with several recognizable functional domains. The protein has a putative signal peptide and transmembrane region, 15 potential sites for N-linked glycosylation, and 12 C2-type immunoglobulin (Ig)-like domains. All of the Ig-like domains contain the two conserved cysteine residues that form intradomain disulfide bonds typical of this superfamily. These features are consistent with a possible role for this molecule in cell surface recognition or cell-cell interaction.

Amino Acid Sequence↗

Glycoinositol phospholipids from Endotrypanum species express epitopes in common with saccharide side chains of the lipophosphoglycan from Leishmania major.

We have characterized glycoinositol phospholipids (GIPLs) from three strains of the trypanosomatid parasites Endotrypanum schaudinni and Endotrypanum monterogeii. Methanolysis of the intact GIPLs liberated methyl esters of tetracosanoic acid, docosanoic acid, octadecanoic acid and hexadecanoic acid and C20 and C21 phytosphingosines. Phosphoinositol oligosaccharides were released from the GIPLs by mild base treatment, and their structures were determined by compositional analysis, fast-atom-bombardment MS and NMR spectroscopy. Similar compounds were detected in all three strains, although their relative proportions varied. The predominant components in E. schaudinni strain LV59 and E. monterogeii LV88 were Galpbeta1-3Galpbeta1-3Manalpha1-3Manalpha1-4G lcNalpha1-6Ins-1-P and Arapbeta1-2Ga lpbeta1-3Galpbeta1-3Manalpha1-3Manalpha1-4Glc Nalpha1-6Ins-1-P, and the major phosphoinositol oligosaccharide in E. schaudinni LV58 was the hybrid-type GIPL Manalpha1-2(EtNP-6)Manalpha1-6(Galpbeta1-3Man alpha1-3)Manalpha1-4GlcN alpha1-6Ins-1-P (where EtNP is ethanolamine phosphate). Several minor oligosaccharides containing additional galactose and/or arabinose residues were also detected.

Animals↗

Structural mobility in deglutition after single modality treatment of head and neck carcinomas with radiotherapy.

BACKGROUND: The results of a preliminary study designed to evaluate swallowing function in patients 1 year after successful treatment of head and neck carcinomas with radiotherapy are reported. METHODS: Movement of the velum, hyoid, larynx, tongue base, and posterior pharyngeal wall were objectively assessed by dynamic videofluoroscopy. Mean values of each swallowing parameter measured from the study group were compared with normative data from a group of 60 normal control subjects. The radiotherapy patient group was divided based on the location of the primary tumor in an attempt to correlate the effect of tumor location on swallowing. RESULTS: Hyoid displacement was decreased in radiotherapy patients and the hyoid elevated maximally independent of bolus size, unlike control subjects, in whom hyoid displacement increased with increases in bolus size. Patients with tongue base tumors demonstrated decreased pharyngeal constriction compared with patients with larynx and pharynx/nasopharynx tumors. CONCLUSIONS: A generalized decrease in the mobility of pharyngeal structures is demonstrated after radiotherapy.

Deglutition↗

Similarity of monosaccharide, oligosaccharide and polysaccharide structures in gum exudate of Anacardium occidentale.

The gum exudate from the Brazilian cashew-nut tree (Anacardium occidentale) contained traces of the reducing sugars, rhamnose (0.005%), arabinose (0.03%), mannose (0.007%), galactose (0.03%), glucose (0.02%), beta-D-Galp-(1-->6)-alpha beta-D-Gal (0.05%), alpha-L-Rhap-(1-->4)-alpha beta-D-GlcA (0.008%) and alpha-L-Rhap-(1-->4)-beta-D-GlcpA-(1-->6)-beta-D-Galp-(1-->6 )-alpha beta-D-Gal (0.008%). Rhamnose, arabinose, glucose and the three oligosaccharides are components of the side-chains of the gum polysaccharide, which has a main chain of (1-->3)-linked beta-D-Galp units. The structure of this polysaccharide was determined and found to differ from that previously reported for the gum of a tree growing in India, lacking units of 4-O-methylglucuronic acid. Other new side-chain structures were characterized, particularly -alpha-D-Galp-(1-->6)-D-Galp- and alpha-L-Araf-(1-->6)-D-Galp-).

Carbohydrate Sequence↗

Gum heteropolysaccharide and free reducing mono- and oligosaccharides of Anadenanthera colubrina.

The gum from Anadenanthera colubrina consists mainly of a complex high-arabinose heteropolysaccharide with a (1-->3)-linked beta-D-Galp main-chain and many different side-chains. These contain beta-D-Galp-[(1-->6)-beta-D-Galp]m-(1-->6)-, substituted in turn at O-3 by alpha-L-Araf-[(1-->3)-alpha-L-Araf-]0-2. Also present are (1) main-chain units substituted at O-4 and O-6 by alpha-L-Araf units, (2) side-chains of Rhap-(1-->4)-beta-D-GlcpA-(1-->6)-beta-Galp-groups, (3) alpha-L-Arap non-reducing end-units linked (1-->6) to D-Galp, and (4) beta-Araf and beta-Arap structures. For the first time, a plant gum exudate was found to contain in the natural state, reducing low M(r) carbohydrates. These were rhamnose (0.6%), arabinose (4.7%), mannose (0.1%), galactose (0.8%) and many oligosaccharides (0.6%; 11 with different RFs, with the majority containing arabinose). They were all mixtures with the exception of alpha-Rhap-(1-->4)-beta-D-GlcpA-(1-->6)-alpha beta-Gal and an incompletely identified hexasaccharide, probably having alpha-L-Araf-(1-->4)-beta-D-Galp- and -alpha-L-Araf-(1-->3)-beta-D-Galp- structures. The mono- and oligosaccharides do not appear to arise via in situ autohydrolysis of the gum.

Carbohydrate Conformation↗

Bi-exponential T2 decay in dairy cream phantoms.

MRI phantoms are an important part of any experiment because they provide a reference of known parameters. There are many choices of mono-exponential T2 phantoms, but few choices for bi-exponential T2 phantoms. We have found that dairy cream provides an excellent bi-exponential T2 model with similar relaxation times to those found in white matter. Five cream phantoms of different milk fat percentages (2, 6, 10, 18 and 35 %) were imaged with an optimized Carr-Purcell-Meiboom-Gill sequence. The decay curves for each of the phantoms were fit using Non-Negative Least Squares. We found that the short T2 component fraction relative to the total energy in the distribution correlated linearly (r = 0.9973) with the milk fat percentage. The short T2 time was 38+/-4 ms and the long T2 time was 135+/-4 ms.

Brain↗

Is a murder charge an occupational hazard of intensive care nursing?

When nurses are accused of harming their patients there is an understandable wave of concern. When nurses kill their patients there is disbelief and horror. After all, killing patients is so far from the traditional image of the nurse as to cause distress and disorientation. When the nurse in question is a woman and when the charge amounts to serial killing, our most cherished assumptions about gender roles and professional responsibility are called into question. Yet in this decade nurses have been accused of killing patients, attempting to kill patients and causing grievous bodily harm to others. In the UK, of the nurses accused of attempting to murder their patients two came from the same specialism. Two of the three accusations centred on Intensive Care Units (ICU); the case of Amanda Jenkinson (Kenny 1996) and the case of Kath Atkinson, an ICU sister in Newcastle (Porter 1998a). In the most notorious case of nurse homicide in the UK this decade, that of paediatric nurse Beverly Allitt, the profession and society at large were shaken by accusations so serious as to defy belief.

Criminal Psychology↗

Inhaled nitric oxide: are the safety issues being addressed?

Interest in the therapeutic uses of Nitric Oxide (NO) has gathered pace over the last decade. It is no exaggeration for the UK Guidelines on the Use of Inhaled Nitric Oxide (Cuthbertson et al. 1997) to say that 'the use of inhaled nitric oxide in the UK has become commonplace'. The index of the third edition (1990) of TE Oh's notable Intensive Care Manual carries no reference to it. Yet, from its origins in obscure research, the discovery of NO has promised the development of therapies which might include the revolutionary transformation of approaches to the treatment of septic shock. It also holds promise in the treatment of acute respiratory distress syndrome (ARDS). It is in this context that this discussion will seek to raise fundamental questions about the health and safety aspects of this substance.

Administration, Inhalation↗

Tissue-specific expression of human salivary mucin gene, MUC7, in transgenic mice.

The MUC7 gene encodes the protein core of the low molecular weight human salivary mucin (MG2, mucin glycoprotein 2) and is expressed in a tissue-specific manner in salivary glands. The purpose of this study was to examine MUC7 expression by transgenic mouse technology. A 16 kb DNA fragment, containing the MUC7 gene (10 kb) and 3 kb of the upstream and 3 kb of the downstream sequences, was used to generate transgenic mice. We have identified five transgenic founder mice which were propagated as individual transgenic lines and analysed. Tissues of transgenic offspring from each line were analysed by RT-PCR to determine the sites of the MUC7 expression. The results indicated that only line 3 and line 5 expressed the MUC7 gene in salivary glands. The level of MUC7 expression in selected tissues was then determined by northern blot analyses. The results showed that line 3 mice contained high levels of MUC7 transcripts in the sublingual glands of both males and females and indicated low levels of MUC7 transcripts in the submandibular glands of females. No MUC7 expression was detected in this line by northern blot analysis in any other tissue tested. On the other hand, no expression of MUC7 was detected in any tissues of line 5 mice examined by northern blot analysis. A Southern blot analysis of human and mouse genomic DNA demonstrated multiple copies of the MUC7 transgene in line 3 and a single copy in line 5. Collectively, these results indicate that the regulatory sequences required for the tissue-specific expression of MUC7 are within the MUC7 transgene. However, the sequences necessary for expression comparable to that of MUC7 in human salivary glands may be missing from this construct. Western blot analysis of protein extracts from different tissues of transgenic mice line 3 showed that MUC7 gene product was produced in the submandibular-sublingual gland complex of both male and female mice and not in the other tissues examined.

Animals↗

Beta-amyloid augments platelet aggregation: reduced activity of familial angiopathy-associated mutants.

The beta-amyloid (A beta) peptide is present both in serum and in platelets, however it is unclear whether A beta plays a role in platelet function. We have now investigated the effects of soluble A beta on platelet function and have found that low levels (0.1-1 nM) of soluble A beta augment ADP-dependent platelet aggregation and translocation of focal adhesion kinase to the platelet cytoskeleton. Addition of A beta to gel-filtered platelets along with concentrations of adenosine diphosphate (ADP) producing submaximal aggregation responses increased the aggregation response by over 2-fold depending on the ADP:A beta ratios. The structure activity requirements for A beta activity showed intriguing constraints. Only full length A beta has significant activity. Truncated A beta peptides, such as A beta(1-16) or A beta(25-35), or reverse A beta(40-1) all show little or no activity. We also examined the activity of mutant A beta peptides, corresponding with the APP(692A-G) and APP(693E-Q) (at A beta21 and A beta22, respectively) which are found in familial Alzheimer's disease and hereditary cerebral hemorrhagic amyloidosis, Dutch type (HCHWA-D), and found that these peptides showed little or no activity. These results suggest that A beta interacts with platelets in a highly specific manner and may play a role in regulating platelet function.

Adenosine Diphosphate↗

New gene assignments using a complete, characterized sheep-hamster somatic cell hybrid panel.

The generation and characterization of new sheep-hamster cell hybrids is reported from the fusion of sheep white blood cells with six different hamster auxotrophs. Selection from these and previously generated cell hybrids has led to the production of a panel of 30 hybrids covering the complete sheep genome of 28 chromosomes. Over half of the cell hybrids in this panel contain single sheep chromosomes. By complementation, the following new assignments have been made using the panel: phosphoribosyl N-formylglycinamide amidotransferase (PRFGA) to sheep chromosome (chr) 11; adenylosuccinate synthetase (ADSS) to sheep chr 12; adenylosuccinate lyase (ADSL) to sheep chr 3q; 3-hydroxy-3-methylglutaryl-coenzyme A synthase (HMGCS) to sheep chr 16; dihydrofolate reductase (DHFR) to sheep chr 5; and adenine phosphoribosyltransferase (APRT) to sheep chr 14. The gene phosphoribosylaminoinidazole-carboxamide formyltransferase/Inosinicase (PRACFT) has now been regionally assigned to chr 2q. By isozyme analysis, phosphogluconate dehydrogenase (PGD) was assigned to sheep chr 12, anchoring the sheep syntenic group U1 to this chromosome, and mannose phosphate isomerase (MPI) was assigned to sheep chr 18. Furthermore, the chromosomal assignment of 110 microsatellites was confirmed using this cell panel.

Adenine Phosphoribosyltransferase↗

Creatinine clearance as a measure of GFR in screenees for the African-American Study of Kidney Disease and Hypertension pilot study.

Serum creatinine and endogenous creatinine clearance (CrCl) are widely used measures of renal function. This study compares the precision, bias, and sources of error in using different CrCl measures to estimate the glomerular filtration rate (GFR) in 118 men and women screened for the African-American Study of Kidney Disease and Hypertension (AASK) pilot study. We measured serum creatinine, 24-hour CrCl, and CrCl during timed clearance periods conducted simultaneously with an 125I-iothalamate GFR study. Serum creatinine was measured using two different kinetic rate Jaffe methods (CX3 and Hitachi). After standardization for body surface area, the different measures of renal function available for each individual were compared with the 125I-iothalamate GFR simultaneous to the CrCl. In a subset of 50 participants, the CrCl measures were compared with a follow-up GFR (fGFR). The mean 125I-iothalamate GFR was 65.2 (SD, 26.4), with a range of 11 to 122 mL/min/1.73 m2. The mean +/- SD percentage differences from the GFR were -9%+/-22% for the Cockcroft-Gault estimated CrCl, 1%+/-29% for the 24-hour CrCl, and 8%+/-16% for the CX3 simultaneous CrCl. The Hitachi method overestimated serum creatinine and underestimated GFR. Compared with an fGFR, the mean +/- SD differences were 2%+/-19% for the first GFR, -6%+/-20% for the Cockcroft-Gault estimated CrCl, 10%+/-28% for the 24-hour CrCl, and 14%+/-29% for the CX3 simultaneous CrCl. Thus, the increased precision with which the timed CrCl predicted its simultaneous GFR did not extend to improved ability to predict a future GFR. The fractional excretion of creatinine, measured as the ratio of the CX3 simultaneous CrCl to 125I-iothalamate clearance, increased with decreasing GFR but was lower than expected (mean +/- SD of 1.21+/-0.16 for GFRs between 20 and 40 mL/min/1.73 m2). The lower fractional excretion explains why the 24-hour and Cockcroft-Gault CrCls did not overestimate GFR, but the reasons for this lower excretion are uncertain. Creatinine assay specificity and calibration are important sources of variability that must be examined in any CrCl measure of GFR. We conclude that despite requiring substantially more time and effort, neither the outpatient 24-hour urine nor the timed CrCl offered increased precision over a calculation based on serum creatinine, sex, age, and weight in predicting GFR.

Black People↗

Patient-controlled sedation and analgesia, using propofol and alfentanil, during colonoscopy: a prospective randomized controlled trial.

BACKGROUND AND STUDY AIMS: Patient-controlled sedation (PCS) enables titration of dosage to an individual's requirements and is potentially useful in colonoscopy. The aim was to compare the value of patient-controlled sedation, using propofol and alfentanil, with that of intravenous diazemuls and pethidine during colonoscopy. PATIENTS AND METHODS: Following randomization, 66 patients undergoing colonoscopy received either an intravenous bolus of pethidine (50 mg) and diazemuls (10-20 mg) prior to colonoscopy or were connected to an infusion pump containing propofol (10 mg/ml) and alfentanil (25 microg/ml). Patients self-administered 0.5 ml boluses as often as they required. Pain and sedation score were recorded by a nurse specialist and on a patient questionnaire. An anaesthetist was present throughout the procedure. RESULTS: PCS provided lighter sedation (median sedation score, 3 versus 4; P=0.0001), less analgesia (median pain score, 1 versus 0; P=0.004), a smaller maximum fall in systolic blood pressure (23 mmHg versus 33 mmHg; P=0.02) and a faster recovery time (median 10 min versus 40 min; P=0.0001), irrespective of the dose administered, compared with a diazemuls-pethidine combination. The duration of the procedure was unaffected. All patients were satisfied with their level of sedation. CONCLUSIONS: Patient-controlled sedation is an effective alternative to premedication with narcotic/benzodiazepine combinations during colonoscopy.

Adult↗

Monoclonal antibodies with specificities for Streptococcus pneumoniae group 9 capsular polysaccharides.

Streptococcus pneumoniae group 9 includes four capsular polysaccharide types: 9A, 9L, 9N and 9V. We have generated four mouse monoclonal antibodies against group 9 polysaccharide using heat-treated S. pneumoniae strains of different capsular polysaccharides types as immunogens. The specificities of the monoclonal antibodies were determined by ELISA using capsular polysaccharide directly coated to the wells as antigens and by dot blotting with heat-treated bacteria. Two groups of monoclonal antibodies were found. The first group included two monoclonal antibodies which were found to be capsular type specific. The second group was monoclonal antibodies that bound to epitopes shared by two or three pneumococcal group 9 types. The monoclonal antibody 204,A-4 (IgM) was found to be specific for S. pneumoniae type 9N. The binding of the type 9V specific monoclonal antibody 206,F-5 (IgG1) was found to be dependent upon O-acetyl groups. Monoclonal antibody 205,F-3 (IgM) reacted also with type 9V, but was found to cross-react with types 9A and 9L. The binding of this monoclonal antibody to polysaccharide 9V was not dependent upon O-acetyl moieties. The fourth monoclonal antibody (214,G-5, isotype IgM) did not show any correlation between reactivity with isolated polysaccharides and dot blotting with relevant bacteria. The monoclonal antibody reacted with polysaccharides 9A and 9L in ELISA, but not with the homologous bacteria.

Age Factors↗

A protein encoded by the latency-related gene of bovine herpesvirus 1 is expressed in trigeminal ganglionic neurons of latently infected cattle and interacts with cyclin-dependent kinase 2 during productive infection.

Despite productive viral gene expression in the peripheral nervous system during acute infection, the bovine herpesvirus 1 (BHV-1) infection cycle is blocked in sensory ganglionic neurons and consequently latency is established. The only abundant viral transcript expressed during latency is the latency-related (LR) RNA. LR gene products inhibit S-phase entry, and binding of the LR protein (LRP) to cyclin A was hypothesized to block cell cycle progression. This study demonstrates LRP is a nuclear protein which is expressed in neurons of latently infected cattle. Affinity chromatography indicated that LRP interacts with cyclin-dependent kinase 2 (cdk2)-cyclin complexes or cdc2-cyclin complexes in transfected human cells or infected bovine cells. After partial purification using three different columns (DEAE-Sepharose, Econo S, and heparin-agarose), LRP was primarily associated with cdk2-cyclin E complexes, an enzyme which is necessary for G1-to-S-phase cell cycle progression. During acute infection of trigeminal ganglia or following dexamethasone-induced reactivation, BHV-1 induces expression of cyclin A in neurons (L. M. Schang, A. Hossain, and C. Jones, J. Virol. 70:3807-3814, 1996). Expression of S-phase regulatory proteins (cyclin A, for example) leads to neuronal apoptosis. Consequently, we hypothesize that interactions between LRP and cell cycle regulatory proteins promote survival of postmitotic neurons during acute infection and/or reactivation.

Animals↗

Alternative splicing of the latency-related transcript of bovine herpesvirus 1 yields RNAs containing unique open reading frames.

The latency-related transcript (LRT) of bovine herpesvirus 1 (BHV-1) is the only abundant viral RNA detected during latency. A previous study (A. Hossain, L. M. Schang, and C. Jones, J. Virol. 69:5345-5352, 1995) concluded that splicing of polyadenylated [poly(A)+] and splicing of nonpolyadenylated [poly(A)-] LRT are different. In this study, splice junction sites of LRT were identified. In trigeminal ganglia of acutely infected calves (1, 7, or 15 days postinfection [p.i.]) or in latently infected calves (60 days p.i.), alternative splicing of poly(A)+ LRT occurred. Productive viral gene expression in trigeminal ganglia is readily detected from 2 to 7 days p.i. but not at 15 days p.i. (L. M. Schang and C. Jones, J. Virol. 71:6786-6795, 1997), suggesting that certain aspects of a lytic infection occur in neurons and that these factors influence LRT splicing. Splicing of poly(A)- LRT was also detected in transfected COS-7 cells or infected MDBK cells. DNA sequence analysis of spliced LRT cDNAs, poly(A)+ or poly(A)-, revealed nonconsensus splice signals at exon/intron and intron/exon boundaries. The GC-AG splicing signal utilized by the herpes simplex virus type 1 latency-associated transcript in latently infected mice is also used by LRT in latently infected calves. Taken together, these results led us to hypothesize that (i) poly(A)+ LRT is spliced in trigeminal ganglia by neuron-specific factors, (ii) viral or virus-induced factors participate in splicing, and (iii) alternative splicing of LRT may result in protein isoforms which have novel biological properties.

Alternative Splicing↗