Search PubMed⌕ Search

Biomedical subjects

J Cole

Publications and source records attributed to J Cole.

At least 163 records · Page 9Linked to original sources
PubMed1991

Long-term survival and preservation of natural killer cell activity in a xeroderma pigmentosum patient with spontaneous regression and multiple deposits of malignant melanoma.

A 67-year-old man with xeroderma pigmentosum (XP) originally presented with malignant melanoma at the age of 28 years. This recurred 22 years later and subsequently numerous primary and secondary melanomas developed on the skin, several of which underwent spontaneous regression. Despite a marked lymphopenia, the proportion of natural killer cells was elevated and it is proposed that this led to the regression of the melanomas. Skin-derived fibroblasts from the patient were more sensitive to UVC (D10 approximately 3 J/m-2) than those from normal individuals (D10 approximately 15 J/m-2). The fibroblast culture was shown to be defective in excision repair with less than 10% of residual activity compared with controls. No assignment to a complementation group has yet been made. There was an elevated frequency of mutants resistant to 6-thioguanine in the circulating T lymphocytes.

Adult↗
PubMed1991

Circulating catecholamine concentrations in cocaine-exposed neonates: a pilot study.

Twenty newborns, 12 with prenatal exposure to cocaine and an unexposed control group of 8, were studied to determine concentrations of circulating catecholamines and their relationship to newborn behavior. Birth weight of the cocaine-exposed neonates was significantly lower than that of the control group. Gestational age, length, and head circumference of the cocaine-exposed neonates were also lower, although the differences did not reach statistical significance. Between 24 and 48 hours of age, circulating concentrations of norepinephrine, dopamine, and the catecholamine precursor dihydroxyphenylalanine were measured and behavior was assessed using the Neonatal Behavioral Assessment Scale. Mean dihydroxyphenylalanine concentrations were increased in the cocaine-exposed newborns (10.3 ng/mL vs 5.9 ng/mL, P = .055), while there was no difference between the groups in mean norepinephrine or dopamine concentrations. There was a significant negative correlation between norepinephrine concentration and orientation cluster score for the cocaine-exposed newborns (r2 = .6979, P = .005). norepinephrine concentration did not correlate with the score for any other behavioral cluster, nor did dopamine or dihydroxyphenylalanine concentration correlate with the score for any cluster. These preliminary data from a pilot study suggest that catecholamine activity is increased in cocaine-exposed newborns and may play a role in neurobehavioral disturbances associated with prenatal exposure to this drug.

Birth Weight↗
PubMed1990

Nucleotide sequence, organisation and structural analysis of the products of genes in the nirB-cysG region of the Escherichia coli K-12 chromosome.

The DNA sequence and derived amino-acid sequence of a 5618-base region in the 74-min area of the Escherichia coli chromosome has been determined in order to locate the structural gene, nirB, for the NADH-dependent nitrite reductase and a gene, cysG, required for the synthesis of the sirohaem prosthetic group. Three additional open reading frames, nirD, nirE and nirC, were found between nirB and cysG. Potential binding sites on the NirB protein for NADH and FAD, as well as conserved central core and interface domains, were deduced by comparing the derived amino-acid sequence with those of database proteins. A directly repeated sequence, which includes the motif -Cys-Xaa-Xaa-Cys-, is suggested as the binding site for either one [4Fe-4S] or two [2Fe-2S] clusters. The nirD gene potentially encodes a soluble, cytoplasmic protein of unknown function. No significant similarities were found between the derived amino-acid sequence of NirD and either NirB or any other protein in the database. If the nirE open reading frame is translated, it would encode a 33-amino-acid peptide of unknown function which includes 8 phenylalanyl residues. The product of the nirC gene is a highly hydrophobic protein with regions of amino-acid sequence similar to cytochrome oxidase polypeptide 1.

Amino Acid Sequence↗
PubMed1990

Transcriptional control of the cysG gene of Escherichia coli K-12 during aerobic and anaerobic growth.

The 74-min region of the Escherichia coli chromosome includes five open reading frames of known sequence. The first and last of these genes, nirB and cysG, are transcribed in the same direction and both are essential for NADH-dependent nitrite reductase activity. The functions of the other genes, nirD, nirE and nirC, which are located between nirB and cysG, are unknown. The nirB gene is transcribed from a promoter which is anaerobically induced, expression being dependent on the transcription activator protein, Fnr. Here we show that the nirD, nirE, nirC and cysG genes are also expressed from the nirB promoter. After subcloning cysG, a second promoter was located less than 100 bases upstream of cysG. Two groups of transcription start points separated by 40 bases were detected in this region by S1 mapping. Rates of transcription from the isolated cysG promoter were the same during aerobic growth and anaerobic growth in the presence or absence of nitrite. However, when the nirB gene and its promoter were cloned back upstream from the cysG promoter, the rate of transcription was higher during anaerobic growth than during aerobic growth and was further induced by nitrite. These increases were totally dependent on a functional fnr gene and were shown by S1 mapping experiments to be due to transcriptional read-through from the Fnr-dependent nirB promoter. No promoter activity was associated with DNA fragments between the BamHI site located within the N-terminal coding region of the nirB gene and the cysG promoter located at the C-terminus of nirC.

Aerobiosis↗
PubMed1990

Comparative induction of gene mutations and chromosome damage by 1-methoxy-1,3,5-cycloheptatriene (MCHT), 2. Results using L5178Y mouse lymphoma cells to detect both gene and chromosome damage; validation with ionizing radiation, methyl methanesulphonate, ethyl methanesulphonate and benzo[a]pyrene.

A variation of the mouse lymphoma (L5178Y TK+/(-)-3.7.2c) assay has been developed using a microtiter cloning technique instead of the standard agar method. The cell line has been used to detect both gene mutations (at the Na+/K+ ATPase and thymidine kinase loci) and chromosome damage (micronucleus induction) in the same experiment. The system was validated using gamma-irradiation (a known clastogen), 2 direct-acting mutagens, ethyl and methyl methanesulphonate and an indirect-acting mutagen, benzo[a]pyrene. Using the assay, 1-methoxy-1,3,5-cycloheptatriene was shown to be a clastogenic mutagen in the presence of S9, since a clear dose-dependent increase in micronuclei was observed, mainly small colony thymidine kinase mutants were observed, and no ouabain-resistant mutants were induced, a profile very similar to gamma-irradiation. The results suggest that metabolic activation potential explains the results in the accompanying paper (Asquith et al., 1990). The implications for mutagenicity testing are discussed.

Animals↗
PubMed1990

Genotoxic effects of radiotherapy and chemotherapy on the circulating lymphocytes of breast cancer patients. III: Measurement of mutant frequency to 6-thioguanine resistance.

The mutant frequencies (MF) at the HPRT locus of peripheral blood lymphocytes collected from breast cancer patients before and after treatment according to a defined protocol of the Institut Curie were compared to those from healthy donors. The treatment involved either a local radiotherapy (RT1) followed by a chemotherapy (CT2) or a chemotherapy (CT1) followed by a radiotherapy (RT2). In accord with others, we observed no significant difference in the MF to 6-thioguanine resistance (6TG) in T lymphocytes in the control and breast cancer groups before treatment. When the effect of CT or RT either alone or in combination was analysed, the increase observed in MF can be wholly accounted for by the effect of radiation. In this study, the effect of chemotherapy on mutation did not achieve significance. Circulating T lymphocytes are mainly in the G0 phase of the cell cycle and thus would not be mutated by drugs which preferentially affect dividing cells, whereas such cells could still mutate when submitted to ionizing radiation.

Adult↗
PubMed1990

Immune function, mutant frequency, and cancer risk in the DNA repair defective genodermatoses xeroderma pigmentosum, Cockayne's syndrome, and trichothiodystrophy.

There is evidence for defective DNA repair in xeroderma pigmentosum, Cockayne's syndrome, and trichothiodystrophy, but for increased cancer risk only in xeroderma pigmentosum. Natural and adaptive immune surveillance and mutant frequency to 6-thioguanine resistance in circulating T-lymphocytes were studied in five patients with xeroderma pigmentosum, two with Cockayne's syndrome, and one with trichothiodystrophy. Forty-eight-hour cutaneous hypersensitivity responses to recall antigens excluded anergy and circulating CD3+, CD4+, CD8+, and CD16+ cell numbers were within normal limits in all patients tested, as were proliferative lymphocyte responses to PHA, except in the trichothiodystrophy patient. Proliferative responses to recall antigens (PPD, SKSD, and Candida) showed that all patients responded to one or more antigens. Direct natural killer cytotoxicity measured against the human erythromyeloid leukaemia cell line K562 using a 4-h 51Cr release assay was significantly reduced in xeroderma pigmentosum (specific cytotoxicity less than mean +/- SD greater than 17.4 +/- 9.4 per cent, with effector:target cell ratio of 50:1) compared to normal controls (45.8 +/- 17.8), but normal in Cockayne's syndrome and trichothiodystrophy. Generation of lymphokine activated killer cell activity was normal in the two xeroderma pigmentosum lines tested. The mutant frequency in the xeroderma pigmentosum donors was significantly increased (p less than 0.01) and was elevated in the two Cockayne's syndrome donors, taking age into account. No mutants were observed from the single trichothiodystrophy donor. These findings suggest that reduced natural killer cell activity may contribute to the greatly increased susceptibility to skin cancer in xeroderma pigmentosum.

Antigens, CD↗
PubMed1990

Radiobiological studies in the naevoid basal cell carcinoma syndrome.

The naevoid basal cell carcinoma syndrome is described in a 43-year-old male. The response of dividing fibroblasts from this patient to the lethal effects of ionizing radiation was indistinguishable from that of a normal control: mean inactivation dose (D) = 1.74 Gy and 1.68 Gy, respectively. However, these cells were defective in the repair of potentially lethal damage (D = 2.36 Gy and 3.26 Gy, respectively). The response to radiation of Go T lymphocytes derived from the patient was similar to that of the control. The frequency of mutant circulating T lymphocytes resistant to 6-thioguanine was 17 x 10(-6) which was elevated when compared with age-matched controls. These results suggest an abnormality in the response of the fibroblasts to ionizing radiation damage.

Adult↗
PubMed1990

Stimulation of transient elevations in cytosolic Ca2+ is related to inhibition of Pi transport in OK cells.

Stimulation of changes in cytosolic free calcium by parathyroid hormone was determined in three opossum kidney (OK) cell types, OK wild-type, OKP clone, and OKH clone. All three types of OK cells express parathyroid hormone (PTH)-sensitive adenylate cyclase and adenosine 3',5'-cyclic monophosphate (cAMP) production. However, only the OK wild-type and the OKP clone respond to PTH with inhibition of sodium-dependent Pi transport and transient increase in cytosolic calcium. Characterization of the increases in cytosolic calcium in the wild-type and OKP clones revealed they were due in part to stimulation of Ca2+ release from intracellular stores, probably by inositol 1,4,5-trisphosphate (IP3), which was stimulated by PTH. PTH-stimulated Ca2+ transients were also inhibited by protein kinase C activation. These data are compatible with PTH receptor-mediated phospholipase C activation and its feedback inhibition by protein kinase C. The OKH cells demonstrated a slow increase in cytosolic calcium when stimulated by cyclic nucleotides but no evidence for PTH stimulation of Ca2+ release from intracellular stores. Thus the absence of an inhibitory response of sodium-dependent Pi transport to PTH in the OKH cells is associated with the absence of the rapid transient elevations of cytosolic Ca2+ such as those produced by IP3 production. These data suggest an important cooperative role for cAMP and the phospholipase C-stimulated Ca2(+)-protein kinase C message system in the regulation of Pi transport.

Adenylate Cyclase Toxin↗
PubMed1990

A statistical analysis of the third UKEMS collaborative trial.

In the third UKEMS collaborative trial, nine laboratories optimized protocols for a variety of mammalian cell mutagenicity assays and used these protocols to test three reference mutagens. Data from the trial have been deposited with Mutagenesis under the scheme of the journal for a database of results of extensive mutagenicity testing programmes. A preliminary examination of the data using procedures advocated by the UKEMS guidelines on statistical evaluation of mutagenicity test data confirms that the assays are capable of giving clear, convincing data, in a form amenable to statistical analysis. The utility of the methods of analysis proposed by both the plate and fluctuation test statistical working groups was confirmed. In almost all cases variation between plates or trays from the same replicate treatment was little greater than Poisson or binomial, whereas variation between replicate treatments was substantially larger, confirming the recommendation of both groups for true independent replicates of each treatment. In six out of nine laboratories part of this variation between replicates was consistent for both viability and mutation, which might cause the guide-lines procedure for fluctuation test data to underestimate significance. In about half the cases examined, variation between experiments was significantly greater than variation between replicates within an experiment, which may create problems of interpretation. Supplementary tests, using the statistical package GLIM, suggested that although factors such as choice of expression time, level of S9, zero dose cloning efficiency or spontaneous mutation frequency might have an effect, they would not have been likely to interfere with detection of a mutagenic effect in the present data set.

Analysis of Variance↗
PubMed1990

The third United Kingdom Environmental Mutagen Society collaborative trial: overview, a summary and assessment.

An overview of the results of the third UKEMS collaborative trial with cultured mammalian cells is presented and their implications are discussed. Data suitable for statistical evaluation are generated by using the protocols which have been developed for the trial. The results for the three test compounds, ethyl methane sulphonate, benzo[a]pyrene and benzidine (BZD) from the nine participating laboratories demonstrated the essential requirement for replicate cultures in any adequate experimental design. Amongst the many practical points that are reinforced by this study are: (i) the number of cells to be sub-cultured during expression imposes a severe limitation on the use of surface attached cells; (ii) the importance of a careful determination of toxicity; (iii) that S9 levels may need to be varied; and (iv) that BZD is mutagenic only at the tk locus in L5178Y TK+/- cells. The 32P-post-labelling study with BZD reveals that no detectable DNA adducts were found with this agent even in L5178Y or HeLa cells. Thus the mechanism for mutagenesis in L5178Y cells remains to be elucidated.

Animals↗
PubMed1990

Prolongation of the latency period in preterm premature rupture of the membranes using prophylactic antibiotics and tocolysis.

Mixed results have been obtained in several studies using tocolysis or antibiotics individually in the treatment of premature rupture of membranes (PROM). We compared the outcomes of a management protocol consisting of tocolysis, prophylactic antibiotic administration, and documentation of pulmonary maturity with a control group treated with passive expectant management for premature rupture of membranes. There were 55 women in the treatment group and 57 women in the control group. The mean latent phase (+/- SEM) in the treatment group was 7.34 (+/- 1.25) days compared with 1.86 (+/- .431) days in the control group (P less than .001). Eighteen of 55 patients (33%) in the treatment group were electively delivered after documentation of lung maturity, contributing to a falsely lowered mean latent phase in the treatment group. Twenty-four patients in the treatment group and 6 in the control group had a latent phase of 5 days or greater (P = .00018). There were 9 postpartum infections in the control group and 10 infections in the treatment group (P = NS). There was no difference in the length of latent phase of patients treated with ceftizoxime compared with the other antibiotics used (cefoxitin, cefazolin, ampicillin), although postpartum ceftizoxime was more effective in preventing postpartum infections (1 of 28 vs 9 of 27) (P = .005). There were fewer infected neonates in the study group, but this was not significant. It appears that treatment with this protocol significantly prolongs the latent phase in patients with preterm PROM without increasing infectious morbidity.

Adult↗