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Biomedical subjects

J Cole

Publications and source records attributed to J Cole.

At least 55 records · Page 3Linked to original sources
PubMed1999

Does the oculo-manual co-ordination control system use an internal model of the arm dynamics?

The hypothesis that during self-moved target tracking, the eye-arm co-ordination control system uses an internal model of the arm dynamics was tested. The contribution of arm proprioception to this model was also assessed. Subjects (nine healthy adults and one deafferented subject) were requested to make forearm movements and visually track an arm-driven target. Unexpected changes in mechanical properties of the manipulandum were used to modify the dynamical conditions of arm movement. The smooth pursuit gain (SPG) was computed before and during the perturbation. Results showed a decrease of SPG during perturbation in control subjects only. We propose that an internal model of the arm dynamics may be used to co-ordinate eye and arm movements, and arm proprioception may contribute to this internal model.

Adult↗
PubMed1999

Low alcohol preference among the "high alcohol preference" C57 strain of mice; preference increased by saline injections.

RATIONALE AND OBJECTIVE: This study investigated individual alcohol preference among the "high alcohol preferring" strain of C57BL10 (line ScSn) mice. METHODS: Alcohol preference was assessed in free choice two-bottle preference tests, using 8% ethanol and tap water, under various conditions. RESULTS: Between 15 and 40% of the mice, bred in house, showed a low preference for alcohol with ethanol/water ratios of 0.4 or less. There was a biphasic distribution of preference, and no relationship between alcohol preference and gender. Mice of the C57BL/6 strain from an outside breeder also contained animals with low preference for alcohol. Selective breeding from "in house" stock did not demonstrate evidence of a simple genetic link. Ethanol preference showed no correlation with locomotor activity or the effects of alcohol on such activity. Daily intraperitoneal injections of saline increased the preference of low preference mice, an effect prevented by the CCK(B) antagonist, CAM1028. The preference of "low preference" mice was significantly increased when the effects of saline injections were compared with those of handling alone. Diazepam, at 1 mg/kg, did not affect the low preference, compared with Tween vehicle. This demonstration of C57 strain mice with low preference for alcohol may provide a valuable model for the effects of stress on alcohol consumption.

Alcohol Drinking↗
PubMed1999

Co-cultivation of CD4+ and CD8+ human T-cells leads to the appearance of CD4 cells expressing CD8 through de novo synthesis of the CD8 alpha-subunit.

The appearance of a population of dual-staining CD4+CD8+ cells in human T-lymphocyte cultures has been reported by various authors, including our own observation that they are always seen in simple phytohaemagglutinin-stimulated cultures from several different donors. The purpose of the present study was to investigate factors involved in the dual-staining (DS) phenotype, and to clarify some apparent inconsistencies between published observations. Our findings can be summarised as follows. 1. A population of DS CD4+CD8+ cells always appears in PHA-stimulated T-cell cultures if they contain both CD4 and CD8 subsets. The incidence of DS cells is related to PHA concentration, but other factors are involved since DS cells are not seen in PHA-stimulated cultures of purified CD4+ or CD8+ cells. Stimulation with PHA is not a prerequisite since very similar results are seen with ConA. 2. Direct physical contact between CD4+ and CD8+ cells is required for the appearance of the DS phenotype; soluble factors alone, including IL-4, appear nor to be responsible. 3. The DS phenotype in these conditions is always CD4+ cells weakly expressing CD8 and is a consequence of de novo synthesis of the CD8alpha molecule by the CD4+ cells.

Apoptosis↗
PubMed1999

Regulation of the lipopolysaccharide-specific sialyltransferase activity of gonococci by the growth state of the bacteria, but not by carbon source, catabolite repression or oxygen supply.

The enzyme sialyltransferase (STase) of Neisseria gonorrhoeae is a major pathogenicitiy determinant. Using a refined method for assaying the STase activity, the Km for CMP-NANA was shown to be 14 +/- 2 microM, higher than that reported previously. Rates of sialylation by Nonidet extracts, prepared under conditions that optimise solubilisation of the membrane-bound enzyme, were 6 to 20 nmol of NANA transferred from CMP-14C-NANA onto isolated lipopolysaccharide/min./mg of extracted protein, far higher than the previously reported rates of less than 1 nmol of NANA transferred/min./mg of extracted protein. Gonococci grew more slowly with lactate or pyruvate than with glucose as the carbon source. Although growth with a mixture of limiting concentrations of both glucose and lactate was biphasic, diauxic growth was also found in the control culture supplied with glucose alone. The growth rate in the presence of lactate alone was slower than with glucose. The growth rate increased slightly relative to the glucose culture when both substrates were available; lactate was consumed more rapidly than glucose. Higher STase activities were found in bacteria harvested in the exponential than in the stationary phase of aerobic growth: the activity in aerated cultures was higher than those of oxygen-limited or anaerobic cultures. Similar STase activities were found in bacteria that had been grown with glucose, lactate or pyruvate as the carbon and energy source. Sialyltransferase synthesis is essentially constitutive: it is not regulated by glucose repression or by induction by lactate or anaerobiosis.

Carbon↗
PubMed1999

Underground coal miners' foot and boot problems.

The New South Wales (NSW) Joint Coal Board Health and Safety Trust funded an investigation into foot problems reported by 400 randomly selected underground coal miners from 15 mines in NSW. Miners were interviewed and their responses were entered directly into laptop computers. Digital cameras were also used to take pictures of skin conditions and miners' posture. Observations of the skin results indicate that miners find gumboots to be hot, sweaty and uncomfortable. Skin breakdown and tinea, is frequent and disabling and responsible for absences from the workforce that are costly for both miner and employer. A more comfortable and better designed boot is needed, fabricated in waterproof leather together with socks that 'wick' the moisture away from the foot. Socks worn were of varying components and washed at irregular intervals, indicating a need for regular changes of socks and improved hygiene.

Coal↗
PubMed1999

ProbeDesigner: for the design of probesets for branched DNA (bDNA) signal amplification assays.

MOTIVATION: The sensitivity and specificity of branched DNA (bDNA) assays are derived in part through the judicious design of the capture and label extender probes. To minimize non-specific hybridization (NSH) events, which elevate assay background, candidate probes must be computer screened for complementarity with generic sequences present in the assay. RESULTS: We present a software application which allows for rapid and flexible design of bDNA probesets for novel targets. It includes an algorithm for estimating the magnitude of NSH contribution to background, a mechanism for removing probes with elevated contributions, a methodology for the simultaneous design of probesets for multiple targets, and a graphical user interface which guides the user through the design steps. AVAILABILITY: The program is available as a commercial package through the Pharmaceutical Drug Discovery program at Chiron Diagnostics.

Animals↗
PubMed1999

Frequencies of hprt(-) mutations and bcl-2 translocations in circulating human lymphocytes are correlated with United Kingdom sunlight records.

Between 1983 and 1995 we have monitored human populations for evidence of exposure to environmental mutagens, taking blood samples to measure hprt(-) mutant frequency in T cells and more recently bcl-2 t(14:18) translocation frequency in B cells. We have now analysed data from 785 assays on 448 blood samples from 308 normal subjects and find that there is a highly significant statistical correlation between hprt(-) mutant frequency and the sunlight record for the 3 weeks prior to taking the blood sample. We discuss the weaknesses in retrospective studies of this nature and the possibility of spurious epidemiological correlations that may result. More controlled experiments can be envisaged that would give a firmer basis to the statistical associations observed. hprt(-) mutations in T cells show little evidence of a UV fingerprint, so that the correlation may be due to immunomodulation rather than mutation. We also find a correlation between the sunlight record and bcl-2 translocation. This translocation is found at a low frequency in the B cells of many normal subjects and is the commonest translocation observed in non-Hodgkin's lymphoma. Our results strengthen the case for a link between sunlight and this increasingly common cancer.

Databases, Factual↗
PubMed1999

Possible effects of sunlight on human lymphocytes.

The human population is exposed to both the ultraviolet A (UVA) and B (UVB) regions of the solar spectrum. UVB induces mainly dipyrimidine photoproducts in DNA by a direct photochemical mechanism, whereas UVA is absorbed by other cellular constituents and induces mainly oxidative damage indirectly. The proportions of the different dipyrimidine photoproducts, and the ratio of dipyrimidine to oxidative damage depend on the exact spectral output of a UV source. Irradiation of human epidermal keratinocytes induces release of cytokines, with cyclobutane pyrimidine dimers playing a significant role in the process. These cytokines may then modulate the activity of cells of the immune system. Freshly isolated human lymphocytes are exquisitely sensitive to UVB irradiation, because of their low deoxyribonucleotide pools. They also have a separate defect in removal of cyclobutane pyrimidine dimers from their DNA. We have observed that frequencies of mutations at the hprt locus in human T-lymphocytes and translocations involving the bcl2 locus in B-lymphocytes appear to be associated with sunlight levels over the period before the blood sample was taken. This may be an indirect cytokine-mediated effect, and may be relevant to the possible link between non-Hodgkin's lymphoma and sunlight. On the other hand, sunlight can have beneficial effects, and may protect against autoimmune diseases including type I diabetes and multiple sclerosis.

Cell Transformation, Neoplastic↗
PubMed1999

Effect of nappy liners on temperature stability in very preterm infants.

OBJECTIVE: To determine whether absorbent liners used in posturally supportive cloth nappies influence temperature stability in infants < 31 weeks gestation. METHODOLOGY: Randomized cross-over trial conducted at King Edward Memorial Hospital for Women, Perth, Western Australia. Twenty-three infants nursed in incubators on Infant Servo Control were randomly assigned to wear cloth postural support nappies alternately with or without absorbent liners for 24-h periods over 4 days. Measurements of skin and incubator temperatures were recorded hourly. Times of all nappy changes and infant handling procedures were also recorded. RESULTS: There was no change in any temperature measurement over time, between days, or between day/night periods. Infants nursed with the liner demonstrated a higher skin temperature (0.04 degrees C), and a lower incubator temperature (1.05 degrees C). A drop in skin temperature of 0.02 degrees C and an increase in incubator temperature of 0.28 degrees C occurred following handling of infants. There was no effect due to sex, gestational age, or actual age of the infants. CONCLUSION: Use of an absorbent liner within a cloth postural support nappy promotes better temperature regulation in infants < 31 weeks gestation, by reducing incubator temperature and increasing skin temperature.

Analysis of Variance↗
PubMed1998

Acute coronary occlusion and in-stent thrombosis in a patient with essential thrombocythemia.

We describe a case of essential thrombocythemia in a 34-year-old male who presented with acute anterior wall myocardial infarction and a platelet count of 2,100,000/mm3. Primary percutaneous coronary angioplasty and stenting were performed. Postangioplasty course was complicated by stent thrombosis requiring repeat coronary angioplasty and persistent femoral arterial bleeding that was treated with surgical exploration and repair. The patient was subsequently treated with platelet pheresis, acetylsalicylic acid, ticlopidine, hydroxyurea, and anagrelide without further complications.

Adult↗
PubMed1998

Hand-mouth coordination, congenital absence of limb, and evidence for innate body schemas.

Studies of phantom limb in cases of congenital (aplasic) absence of limb have provided inadequate evidence concerning the innate neurological substrate responsible for the phantom. In this study we review evidence from ultrasonic and behavioral studies of hand-mouth coordination in utero and in early infancy, neurobiological studies in primates, and studies of neural reorganization following amputation. We suggest two complementary hypotheses to explain aplasic phantoms. First, aplasic phantoms are based on the existence of specific neural circuitry associated with innate motor schemas, such as the neural matrix responsible for early hand-mouth coordination. Second, aplasic phantoms are modified by mechanisms that involve a reorganization of neural representations of the missing limb within a complex network involving both cortical and subcortical structures.

Adolescent↗
PubMed1998

Characterization of a sialyltransferase-deficient mutant of Neisseria gonorrhoeae strain F62: instability of transposon Tn1545 delta3 in gonococci and evidence that multiple genetic loci are essential for lipooligosaccharide sialylation.

Neisseria gonorrhoeae strain JB1 was previously shown to be defective in the sialylation of lipoologosaccharide (LOS) by exogenous CMP-NANA. The LOS components synthesized by the mutant now have been shown by mass spectrometry to be similar to those in the parental strain, F62, and to include the 4.5 kDa widely conserved lacto-N-neotetraose component that can be sialylated. The same two LOS components could be sialylated on the surface of the mutant and parental strains. One major component was sialylatable after chemical extraction of the LOS from either strain. These data confirm that the mutant, JB1, retains the ability to synthesize the LOS target required for the conversion by sialylation of serum-sensitive gonococci to serum resistance. A single base frame-shift mutation was found in the lst gene from the mutant, resulting in the replacement of the final 61 amino acids at the C-terminus of the sialyltransferase by four residues. Seventeen independent clones of the lst gene were isolated from the parental strain, but none of them complemented the sialyltransferase defect of the mutant and no sialyltransferase activity expressed from the clones could be detected in Escherichia coli. Although the data suggest that the mutant might be defective in genes at more than one chromosomal locus and that multiple loci are essential for sialyltransferase synthesis and activity, the alternative possibility, that DNA adjacent to the lst gene encodes a product which is toxic to E. coli, cannot be excluded. The site of insertion of the transposon Tn1545-Delta3 in strain JB1 was cloned and sequenced. The transposon is located in an intergenic region adjacent to genes for a putative ATP-dependent transport protein, but encoding no recognizable function relevant to LOS sialylation. Evidence that transposon Tn1545-Delta3 is unstable in gonococci is presented.

Blotting, Southern↗
PubMed1998

Complexity among constituents of the HLA-B*1501 peptide motif.

Analysis of peptides derived from HLA class I molecules indicates that thousands of unique peptides are bound by a single molecular type, and sequence examination of the pooled constituents yields a motif which collectively defines the peptides bound by a given class I molecule. Motifs resulting from pooled sequencing are then used to infer whether particular viral and tumor protein fragments might serve as class I-presented peptide therapeutics. Still undetermined from a pooled motif is the breadth or range of peptides in the population which are brought together to form the pooled motif, and it is therefore not yet known how representative of the population a pooled motif is. By employing hollow fiber bioreactors for large-scale production of HLA class I molecules, sufficient peptides are produced to investigate individual subsets of peptides comprising a motif. Edman sequencing and mass spectrometric analysis of peptides eluted from HLA-B*1501 reveal that many peptide sequences fail to align with either the N- or C-terminal anchors predicted for the B*1501 peptide motif through whole pool sequencing. These analyses further reveal auxiliary anchors not previously detected and peptides significantly larger and smaller than the predicted nonamer, ranging from 6 to 12 amino acids in length. These results demonstrate that constituents of the B*1501 peptide pool vary markedly in comparison with one another and therefore in comparison with previously established B*1501 motifs, and such complexity indicates that many of the peptide ligands presented to CTL cannot be predicted using class I consensus motifs as search criteria.

Amino Acid Sequence↗