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Biomedical subjects

J Cole

Publications and source records attributed to J Cole.

At least 109 records · Page 6Linked to original sources
PubMed1995

Weight judgment. The discrimination capacity of a deafferented subject.

A weight discrimination study was undertaken to test (i) the capacity of controls and a deafferented subject (deprived of large sensory myelinated fibres from nose down), to discriminate weights with and without vision; (ii) the capacities of observers to discriminate weights while watching the deafferented and control subjects' lifting movements; (iii) the contribution of supplementary sources of sensory information (e.g. vestibular afferents) to the deafferented subject's discrimination capacity. With vision, G.L.'s liminal discrimination of weights was similar to that of the controls. In contrast, precluding vision impaired massively, but not completely, G.L.'s discrimination capacity, so emphasizing the importance of visual kinaesthetic cues in G.L. and incidently the importance of large myelinated sensory function in weight discrimination in controls. Kinematics recordings of G.L.'s lifting movements with vision revealed a significant correlation between weight and peak velocity of the lifting movement. This reflects a specific strategy used by G.L. to generate movements, allowing her to judge the weight of a lifted object visually. Peak velocity rather than amplitude of movement appears to be the main cue for G.L. since there was a lack of correlation between amplitude and weight lifted. For controls, none of the correlations (weight versus amplitude or weight versus velocity) was significant, whether vision was available or not. When watching G.L.'s lifting performance, external observers were able to use similar cues to establish their judgments, but they were far less accurate in doing so when watching control subjects. This suggests that controls were using a strategy different from G.L.'s.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Extended-term cultures of human T-lymphocytes: a practical alternative to primary human lymphocytes for use in genotoxicity testing.

A simplified method, using recombinant interleukin-2, foetal bovine serum and freeze-killed feeder cells, has been developed for the mass culture of T-lymphocytes derived from human peripheral blood. In this protocol, bulk cultures can be cryopreserved approximately 8 days after initiation, and subsequent mass cultures generated a further week after recovery. At the end of this period, the lymphocytes have maintained a normal karyotype and cultures from different donors are very similar in terms of rate of cell division and expression of key antigenic markers. Background micronucleus frequencies and dose-responses for micronucleus induction by a reference clastogen, hycanthone, were also very similar in all the cultures examined. Such extended-term T-lymphocyte cultures are potentially valuable in genotoxicity testing, providing cells with the normal human karyotype which can be characterised and handled with the practical convenience of established rodent cell lines.

Animals↗
PubMed1995

Absence of evidence for mutagenicity of alcoholic beverages: an analysis of hprt mutant frequencies in 153 normal humans.

A substantial database on hprt mutant frequency in circulating T-cells derived from 153 normal humans was analysed to determine if any effect of alcohol consumption could be detected. Alcohol intake (as reported in a questionnaire completed at the time of the blood sample) ranged from 0 to 35+ units per week. Donors were classified into four groups, including total abstainers (n = 18); those who consumed less than the Royal College of Physicians guideline (men, 21 units; women, 14 units) (n = 113); those who consumed more than the guideline value (n = 12); and designated alcohol-dependent subjects (n = 10). No significant difference in mutant frequency between the four groups was found, nor was an overall correlation between alcohol consumption and mutant frequency seen.

Acetaldehyde↗
PubMed1995

Mutant frequencies in workers at the Sellafield installation.

The frequency of hypoxanthine-guanine phosphoribosyltransferase (hprt) mutations has been determined in the peripheral T-lymphocytes of 18 workers at the Sellafield nuclear reprocessing installation with cumulative recorded radiation doses of about 500 mSv or more in comparison with a matched control group of 18 workers with doses less than 50 mSv. The mean dose of the exposed group was 663 mSv (range 449.3-880.8), and of the unexposed group 10.9 mSv (range 0-46.5). During the most recent 6 y the mean doses were 40.1 mSv (range 1.9-93.9) and 2.3 mSv (range 0-8.7), respectively. The logarithmic mean mutant frequency of the exposed group (9.3 x 10(-6)) was lower than that of the unexposed group (12.4 x 10(-6)). The apparent inverse association of mutant frequency and exposure varied in statistical significance tests from borderline to p < 0.01 depending on how the analysis was performed and whether recent or total exposure was considered.

Humans↗
PubMed1995

The biogenesis of c-type cytochromes in Escherichia coli requires a membrane-bound protein, DipZ, with a protein disulphide isomerase-like domain.

A mutant of Escherichia coli K-12, JCB606, which lacks all five c-type cytochromes synthesized during anaerobic growth in the presence of nitrite or trimethylamine-N-oxide (TMAO), was totally defective in Nrf activity and also partially defective in TMAO reductase activity. The mutation in strain JCB606 was shown to affect expression of the tor operon, which contributes almost equally with the products of the dms operon to the rate of TMAO reduction by bacteria during anaerobic growth in the presence of TMAO. The mutation in strain JCB606, dipZ, was mapped by P1 transduction close to the mel operon at co-ordinate 4425 on the E. coli chromosome, the gene order being nrf-fdhF-mel-dipZ-ampC. Recombinant plasmids that restored Nrf activity to test-tube cultures of the mutant were isolated from a cosmid library. A 2.7 kb EcoRV-SmaI fragment (co-ordinates 4443 to 4446 kb on the physical map of the E. coli chromosome) was found potentially to encode three genes arranged in at least two operons. The second gene, dipZ, was sufficient to complement the JCB606 mutation. The translated DNA sequence predicts that DipZ is a 53 kDa integral membrane protein with a 37 kDa N-terminal domain including at least six membrane-spanning helices and a 16 kDa carboxy-terminal hydrophilic domain which includes a protein disulphide isomerase-like motif. It is suggested that DipZ is essential for maintaining cytochrome c apoproteins in the correct conformations for the covalent attachment of haem groups to the appropriate pairs of cysteine residues.

Amino Acid Sequence↗
PubMed1995

Correlation of UVC and UVB cytotoxicity with the induction of specific photoproducts in T-lymphocytes and fibroblasts from normal human donors.

By using specific monoclonal antibodies in situ and a computer-assisted image analysis system we have determined the relative induction of cyclobutane dimers, (6-4) photoproducts and Dewar isomers in human mononuclear cells and fibroblasts following irradiation with UVC, broad-spectrum UVB and narrow-spectrum UVB. The lamps produced these lesions in different proportions, with broad-spectrum UVB inducing a greater combined yield of (6-4) photoproducts and Dewar isomers per cyclobutane dimer than UVC or narrow-spectrum UVB. The relative induction ratios of (6-4) photoproducts compared to cyclobutane dimers were 0.15, 0.21 and 0.10 following irradiation with UVC, broad- or narrow-spectrum UVB, respectively. Although Dewar isomers were induced by UVC, their relative rate of formation compared to cyclobutane dimers was significantly greater after irradiation with either broad-spectrum or narrow-spectrum UVB. These values were 0.001, 0.07 and 0.07, respectively. With each lamp source, we have determined the survival of normal human T-lymphocytes and fibroblasts at fluences, which induce equivalent yields of cyclobutane dimers, (6-4) photoproducts or (6-4) photoproducts plus Dewar isomers. Killing of fibroblasts appears to be associated with (6-4) photoproduct formation, whereas killing of T-lymphocytes seems to be mediated by combined (6-4) plus Dewar yields. These results emphasize the need to study the biological effects of UVB because cellular responses may be different from those following UVC irradiation.

Antibodies, Monoclonal↗
PubMed1995

Saliva stimulants and the oral health of geriatric patients.

Root-surface caries (RSC) has been recognized as a specific and important dental disease. Significant advances have been made in the pathology and microbiology of RSC, and the need to standardize the guidelines for recording RSC data has been recognized. Researchers have emphasized the increasing impact RSC will have on the geriatric population, especially since the methods to treat and prevent this disease are limited. The purpose of this study was to investigate the possibility of limiting RSC in a Veterans Administration (VA) patient population, using polyol-containing saliva stimulants that were voluntarily consumed by residents of a VA Medical Center (VAMC) over a period of from six to 30 months. Another aim was to study the effect of this program on the gingival health of periodontal patients.

Aged↗
PubMed1995

Evaluation of a commercial automated system and software for the identification of veterinary bacterial isolates.

A commercial gram-negative bacterial autoidentification plate was originally developed using bacterial isolates of human origin. Three veterinary diagnostic laboratories conducted a 2-phase trial to enhance the database for veterinary use. The first phase consisted of testing the plate with 447 bacterial isolates of veterinary origin and incorporating that data into the existing database. Emphasis was placed on the Actinobacillus, Bordetella, Pasteurella and Enterobacteriaceae groups, since the Pseudomonas taxon was quite complete. The second phase of the trial consisted of evaluating the enhanced database using 270 clinical veterinary isolates normally encountered in veterinary laboratories. For the Actinobacillus, Bordetella, Pasteurella and Enterobacteriaceae groups, 72% of the bacterial isolates were identified correctly to genus and 85% to species after 18 hours incubation. All identifications in phase 1 and phase 2 were confirmed using conventional methods.

Actinobacillus Infections↗
PubMed1995

Molecular and cellular analysis of the DNA repair defect in a patient in xeroderma pigmentosum complementation group D who has the clinical features of xeroderma pigmentosum and Cockayne syndrome.

Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are quite distinct genetic disorders that are associated with defects in excision repair of UV-induced DNA damage. A few patients have been described previously with the clinical features of both disorders. In this paper we describe an individual in this category who has unusual cellular responses to UV light. We show that his cultured fibroblasts and lymphocytes are extremely sensitive to irradiation with UV-C, despite a level of nucleotide excision repair that is 30%-40% that of normal cells. The deficiency is assigned to the XP-D complementation group, and we have identified two causative mutations in the XPD gene: a gly-->arg change at amino acid 675 in the allele inherited from the patient's mother and a -1 frameshift at amino acid 669 in the allele inherited from his father. These mutations are in the C-terminal 20% of the 760-amino-acid XPD protein, in a region where we have recently identified several mutations in patients with trichothiodystrophy.

Cells, Cultured↗
PubMed1994

Mutation in dipZ leads to reduced production of active human placental alkaline phosphatase in Escherichia coli.

We have tested the expression of alkaline phosphatases in a mutant strain of Escherichia coli deficient in dipZ, a gene coding for a protein involved in cytochrome c biogenesis, and the isogenic wild-type strain. The yield of soluble and active human placental alkaline phosphatase was significantly reduced in the mutant but could be fully recovered by expression of dipZ subcloned in a vector with low copy number. Overexpression of E. coli alkaline phosphatase was unaffected in the mutant with or without dipZ co-expression.

Alkaline Phosphatase↗
PubMed1994

Behavioral effects of smokeless tobacco on the neonate and young Sprague Dawley rat.

Three dosages of Smokeless Tobacco (ST) extract were given to pregnant Sprague-Dawley rats by oral gavage on gestational days (GD) 6-20. The three dosages contained ST extract equivalent to 1.33 mg/kg nicotine (STD-1), 4.0 mg/kg nicotine (STD-2), and 6.0 mg/kg nicotine (STD-3). Dams were intubated three times per day at 8 a.m., 11 a.m., and 2 p.m., providing total daily ST dosages of 4 mg/kg, 12 mg/kg, and 18 mg/kg, respectively. Controls received equivalent volumes of water by gavage. Dams were allowed to deliver, and all biological mothers raised their own pups. On postnatal day 1 (PND 1), litters were culled to 4 +/- 1 females and 4 +/- 1 males. Weights, physical landmark development, and behavioral performance of pups were monitored during pre- and post-weaning periods. Behavioral tests included surface righting, negative geotaxis, swimming development, open field activity, and active avoidance in shuttle box. Our results show that the two higher doses resulted in reduced maternal weight gain. During the pre-weaning period, significant pup weight reductions were noted in the STD-2 pups until PND6, and in the STD-3 group until PND15. In the STD-1 group no statistically significant weight reduction was noted on PNDs 1 and 3, but starting with PND6, pup weights surpassed control group weights. This weight difference persisted throughout the post-weaning period also (P < .05 on PND30 and PND42). The STD-3 pup weights continued to be consistently and significantly (P < .05) reduced throughout the post-weaning period (except on PND24); likewise, the STD-2 pups continued to have lower weights, but at a significant level (P < .05) on PND30 only. The incidence of deaths was increased in a dose-related manner. No significant differences were noted for pinna detachment and incisor eruption; however ST-treatment was significant in affecting earlier eye opening and vaginal patency. N significant ST treatment effects were seen on negative geotaxis, but for surface righting a decreased success rate was noted for the ST-treated groups. Significant differences were noted in swimming development, with the STD-2 pups performing best. Open field activity, as expected, increased from the pre-weaning to post-weaning periods. During the pre-weaning period the STD-3 pups were more active, and during post-weaning the STD-1 pups were more active, but no differences were noted in vertical activity or in the number of stereotypical movements. No treatment-related differences were noted in the active avoidance shuttle box.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Orienting of attention in deafferented patients.

Visual attentional processes were compared in two deafferented patients and 11 normal subjects. Two consecutive stimuli were presented in rapid succession in one of two locations. A peripheral cue first oriented attention to one location where a response was requested. After 100 msec, a second response was required at either the same or opposite location (valid vs invalid cue). Four probabilities of valid cue occurrence were presented: 100, 80, 50 and 20%. Results showed (1) faster reaction times for the second response on cued than on uncued signals; (2) greater attentional effects with increased cue probability; (3) smaller attentional effects in patients. These findings suggest that the patients adopted a cost-minimizing strategy.

Adult↗
PubMed1994

Effect of diet and vitamin C on DNA strand breakage in freshly-isolated human white blood cells.

We have measured DNA strand breaks induced by ionising radiation in nucleated cells from freshly isolated whole blood from normal human subjects. Samples were taken after subjects had fasted overnight and again 1 h after they had eaten breakfast in combination with approximately 35 mg/kg vitamin C. Damage was measured by single cell gel electrophoresis (the 'comet' assay), in which DNA single strand breaks generate a comet tail streaming from the nucleus. In repeat experiments on 6 subjects a reduction in DNA damage, as indicated by a highly significant decrease in overall comet length, was observed following vitamin C ingestion, both in the unirradiated control blood samples and in the dose response to ionising radiation damage. In addition, consistent differences in dose response between individual subjects were found. The peak effect was 4 h after intake of food and vitamin C. An effect was also seen with vitamin C alone and after breakfast without additional vitamin C. Protection against strand breakage was also seen in Ficoll-separated mononuclear cells but evidence was not obtained for protection of separated, mitogen stimulated T-lymphocytes either against ionising radiation cell killing in a clonal assay, or against clastogenicity assessed by micronucleus formation following one cell division. Exposure of separated lymphocytes in vitro to vitamin C, at doses greater than 200 microM, did not offer protection but induced strand breakage. Our results raise the possibility that variation in normal diet may not only affect susceptibility to endogenous oxidative damage, but may affect some responses of the individual to radiation.

Artifacts↗