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Biomedical subjects

F M Ross

Publications and source records attributed to F M Ross.

At least 19 recordsLinked to original sources
PubMed1998

The effects of adenine dinucleotides on epileptiform activity in the CA3 region of rat hippocampal slices.

Alpha, omega-adenine dinucleotides (Ap(n)A) consist of two adenosine molecules linked at the 5' position by phosphate groups, the number of which is denoted by n and can range from 2 to 6. The aim of this study was to investigate the effect of Ap4A and Ap5A on the rate of epileptiform activity. Hippocampal slices (450 microm), when perfused with a medium containing no added magnesium and 4-aminopyridine (50 microM), generate epileptiform activity of an interictal nature. Ap4A and Ap5A at 1 microM depressed the discharge rate to a significant extent. At this concentration adenosine (1 microM) did not produce any effect. However at 10 microM adenosine, Ap4A and Ap5A all decreased the burst frequency. Adenosine deaminase (0.2 U/ml) totally annulled the inhibition of epileptiform activity produced by 10 microM adenosine or 1 microM Ap4A and Ap5A. Adenosine deaminase did not significantly change the maximum depression of activity produced by 10 microM Ap4A and Ap5A. 8-cyclopentyl-1,3-dimethylxanthine, an A1, receptor antagonist, increased the basal rate of epileptiform activity and prevented the depression of burst discharges by Ap4A. 5'-adenylic acid deaminase converts AMP into IMP which is inactive. 5'-adenylic acid deaminase did not prevent the inhibitory effects of Ap4A. The results suggests that in the CA3 region of the hippocampus, Ap4A and Ap5A act partly by stimulating xanthine-sensitive receptors directly and partly through the formation of the metabolite, adenosine.

AMP Deaminase↗
PubMed1998

Modulation by adenine nucleotides of epileptiform activity in the CA3 region of rat hippocampal slices.

1. Hippocampal slices (450 microm) generate epileptiform bursts of an interictal nature when perfused with a zero magnesium medium containing 4-aminopyridine (50 microM). The effect of adenine nucleotides on this activity was investigated. 2. ATP and adenosine depressed this epileptiform activity in a concentration-dependent manner, with both purines being equipotent at concentrations above 10 microM. 3. Adenosine deaminase 0.2 u ml(-1), a concentration that annuls the effect of adenosine (50 microM), did not significantly alter the depression of activity caused by ATP (50 microM). 4. 8-Cyclopentyl-1,3-dimethylxanthine (CPT), an A1 receptor antagonist, enhanced the discharge rate significantly and inhibited the depressant effect of both ATP and adenosine such that the net effect of ATP or adenosine plus CPT was excitatory. 5. Several ATP analogues were also tested: alpha, beta-methyleneATP (alpha, beta-meATP), 2-methylthioATP (2-meSATP) and uridine triphosphate (UTP). Only alpha, beta-meATP (10 microM) produced an increase in the frequency of spontaneous activity which suggests a lack of involvement of P2Y or P2U receptors. 6. Suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), P2 receptor antagonists, failed to inhibit the depression produced by ATP (50 microM). The excitatory effect of alpha, beta-meATP (10 microM) was inhibited by suramin (50 microM) and PPADS (5 microM). 7. ATP therefore depresses epileptiform activity in this model in a manner which is not consistent with the activation of known P1 or P2 receptors, suggesting the involvement of a xanthine-sensitive nucleotide receptor. The results are also indicative of an excitatory P2X receptor existing in the hippocampal CA3 region.

Adenine Nucleotides↗
PubMed1998

Adenosine monophosphate as a mediator of ATP effects at P1 purinoceptors.

1. When perfused with a medium containing no added magnesium and 4-aminopyridine (4AP) (50 microM) hippocampal slices generated epileptiform bursts of an interictal nature. We have shown in a previous study that adenosine 5'-triphosphate (ATP) depressed epileptiform activity and that this effect was blocked by the adenosine A1 receptor antagonist cyclopentyltheophylline but was not affected by adenosine deaminase. This implied that ATP might act indirectly at P1 receptors or at a xanthine-sensitive P2 receptor. The aim of the present study was to investigate further the action of ATP on epileptiform activity. 2. ATP can be metabolized by ecto-nucleotidases to adenosine 5'-diphosphate (ADP), adenosine 5'-monophosphate (AMP) and adenosine, respectively. Each of these metabolites can activate receptors in its own right: P2 receptors for ADP and P1 receptors for AMP and adenosine. 3. We now show that both AMP and ATP (50 microM) significantly decrease epileptiform discharge rate in a rapid and reversible manner. 5'Adenylic acid deaminase (AMP deaminase, AMPase) (0.2 u ml(-1)), when perfused alone did not significantly alter the discharge rate over the 10 min superfusion period used for drug application. When perfused concurrently with AMP (50 microM), AMP deaminase prevented the depressant effect of AMP on discharge rate. 4. AMP deaminase, at a concentration of 0.2 u ml(-1) which annulled the effect of AMP (50 microM), prevented the inhibitory activity of ATP (50 microM). A higher concentration of ATP (200 microM) depressed the frequency of spontaneous bursts to approximately 30% control and this response was also prevented by AMP deaminase. 5. Superfusion of the slices with 5'-nucleotidase also prevented the inhibitory activity of ATP on epileptiform discharges. 6. The results suggest that AMP mediates the inhibitory effects of ATP on epileptiform activity, a conclusion which can explain the earlier finding that cyclopentyltheophylline but not adenosine deaminase inhibited the effect of ATP. A corollary to this is that, when examining the pharmacology of ATP, care must be taken to inactivate AMP with AMP deaminase, as well as adenosine with adenosine deaminase, before a direct action of ATP on P1 receptors can be postulated. Failure to do so may have led to erroneous conclusions in some previous studies of nucleotide activity on nucleotide receptors.

5'-Nucleotidase↗
PubMed1996

Classification of deletions and identification of cryptic translocations involving 7q by fluorescence in situ hybridization (FISH).

Monosomy 7 (-7) and deletion of the long arm of chromosome 7, del(7q), are frequent non-random findings in the myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML), particularly associated with therapy-related disease (t-MDS and t-AML). The cytogenetic breakpoints of 7q deletions are variable, with both terminal and interstitial deletions reported. It is now believed that most deletions are interstitial, and that the variability in reported breakpoints may be due to the difficulty in determining whether the terminal, pale staining G band is present. It has also been suggested that some reported deletions of 7q may be cryptic translocations. To address these questions, we carried out fluorescence in situ hybridization (FISH) studies on leukaemic cells from a large series of patients using a chromosome 7-specific paint and a 7q telomere-specific probe. Of the 26 cases studied, seven were 'pure' deletions (ie without the involvement of other chromosomes); four were interstitial and two terminal. One further patient had two clones each with a different deletion: one with a terminal del(7)(q22) and the second with an interstitial del(7)(q32-qter). A further nine cases had unbalanced translocations with deletion of 7q terminal sequences. The remaining 10 cases were translocations and complex rearrangements, some involving interstitial deletions of 7q. In two cases in which del(7q) was reported as the sole cytogenetic abnormality by G-banding, FISH revealed cryptic translocations involving 7q.

Adult↗
PubMed1995

Development and validation of the Curtin Back Screening Questionnaire (CBSQ): a discriminative disability measure.

Disability accompanying occupational low back pain (LBP) can include a wide range of incapacitating symptoms which, for the practitioner, can be time-consuming and difficult to identify systematically. A questionnaire designed for case-finding and assessment could assist in both the early recognition of disability and in planning management. A suitable questionnaire for clinical use could not be found in the literature. The Curtin Back Screening Questionnaire (CBSQ) was developed, therefore, as a discriminative screening instrument to serve this purpose. The methods and results of the development and validation of the CBSQ are presented herein. Development of the questionnaire followed the principles of Kirschner and Guyatt (1985) employing data from 74 subjects with at least moderately severe work-related LBP. The research design for the validation was multiple-group repeated-measures with a study population of 150 subjects. The screening function of the questionnaire was developed through selecting 8 questions from the whole questionnaire using regression analysis. The questionnaire includes 79 items based on the subjects' perceived health status. The response structure of the CBSQ has been adapted from that of the General Health Questionnaire (GHQ) and some items in the CBSQ have been developed from items in the Sickness Impact Profile (SIP) and GHQ. The questionnaire discriminates effectively between subjects with different degrees of disability, it correlates quite well with the SIP, test-retest reliability for the whole questionnaire is 0.98, the receiver-operating characteristics are more favourable than those for the SIP, and the CBSQ screening score provides an index of severity which correlates with work incapacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Comparison of age-related changes in short-wavelength-sensitive cone thresholds between normals and patients with primary open-angle glaucoma.

PURPOSE: To establish the effect of aging upon short-wavelength-sensitive cone (S-cone) sensitivity for both normals and patients with primary open-angle glaucoma (POAG). METHODS: S-cone thresholds were established for the detection of blue test spots on a bright yellow adapting background. Detection thresholds for combined medium- and long-wavelength-sensitive cones (M/L-cones) were also established for a yellow test spot upon a yellow background. A group of 177 normal subjects (age range 20 to 80 years) and 46 glaucoma subjects were examined. RESULTS: The rate of decline of S-cone sensitivity with increasing age was found to be similar in patients with POAG and age-matched normals (approximately 0.2 log units/decade), although S-cone sensitivity in the POAG population was significantly lower (p < 0.05) than that in age-matched normals by approximately 0.3 log units. CONCLUSIONS: The results of the present investigation show an age-related decline in S-cone sensitivity for both normals and patients with POAG. The decline in S-cone sensitivity within the POAG population is similar to that occurring in normal subjects when the two populations are matched for age.

Adult↗
PubMed1995

Detection of minimal residual disease in childhood acute lymphoblastic leukaemia using fluorescence in-situ hybridization.

Using centromere-specific probes and a fluorescence in-situ hybridization (FISH) technique in cases of childhood hyperdiploid acute lymphoblastic leukaemia (ALL), cells with extra copies of chromosomes can be differentiated from normal cells by their extra signals in both metaphase and interphase nuclei. In this way the entire cell population, not only those cells in division, can be analysed, thereby providing a valuable technique not only for determining leukaemia cell karyotype at diagnosis but also for the detection of minimal residual disease (MRD). We have conducted 161 analyses of remission bone marrow aspirates (BMs) in 13 children with hyperdiploid ALL. Slides were analysed blind and in parallel to 35 control samples. Control BMs showed very low numbers of trisomic cells (mean +/- 2 x SD = 0.13 +/- 0.34%). MRD was detected in 5/13 cases of ALL investigated while on chemotherapy. One out of five newly diagnosed cases and all three relapse cases of ALL had significantly raised levels of hyperdiploid cells in day 28 BMs. The presence of detectable disease in day 28 BMs suggests the need for larger studies to find whether this data is of prognostic value.

Child↗
PubMed1995

t(8;21) myelodysplasia, an early presentation of M2 AML.

The reciprocal translocation of genetic material between chromosomes 8 and 21, t(8;21), is usually restricted to cases of acute myeloid leukaemia (AML). Cases of AML with t(8;21) exhibit characteristic dysplastic features in myeloid and erythroid lineages with reduction in megakaryocytes. We report details of three patients presenting with myelodysplastic features; two had a typical t(8;21), and the third had a variant t(8;21) translocation. We discuss the significance of t(8;21) in the aetiology of myelodysplastic syndrome (MDS) and implications for the management of such patients.

Adult↗
PubMed1995

Detection of t(14;18) in British follicular lymphoma using cytogenetics, Southern blotting and the polymerase chain reaction.

Cytogenetics, Southern blotting and PCR were used to detect t(14;18) in 72 British patients with follicular lymphoma. The overall incidence of the translocation was 76%. Cytogenetics was the most successful technique, but 10-30% of translocations detected karyotypically were missed by molecular methods, presumably due to break-points falling outside the range of probes and primers used here. Reliance on molecular detection alone may considerably underestimate the incidence of t(14;18) and it is therefore essential to use the most comprehensive range of probes and primers available.

Base Sequence↗
PubMed1995

Standardized Assessment for Elderly People (SAFE)--a feasibility study in district nursing.

Current policy requires systematic and comprehensive assessment of elderly people. Few standardized tools exist for assessment. This paper is in two parts. First it reports on the SAFE assessment measures agreed by a multidisciplinary working party initiated by the Royal College of Physicians and the British Geriatrics Society in 1992. The second part reports the findings of a feasibility study of SAFE in district nursing practice. The outcomes examined were the proportion of patients with completed assessments, the time taken to carry out the assessments, acceptability to the patient, carer and district nurse, and the training required. The findings show that SAFE is a practical and acceptable set of instruments in the assessment of elderly people by district nurses, but that further refinement is desirable.

Aged↗
PubMed1994

Practice nurses: characteristics, workload and training needs.

AIM: This study set out to identify the present and future training needs of practice nurses in South West Thames Regional Health Authority and to examine these needs within the nurses' current and changing workloads and social, educational and occupational profiles. METHOD: A questionnaire was sent to 899 practice staff identified by family health services authority records whose salaries were in part reimbursed and in whose job title the word nurse appeared. The questionnaire enquired about personal and practice demography, tasks and activities currently undertaken, perceived role development and training requirements, and preferred organization of training. RESULTS: A total of 620 completed questionnaires were returned (69%). Nurses' work involved treatments, immunizations investigations, administration, first contact with patients, support to the general practitioner and health promotion. The areas of role development selected most commonly by nurses were counselling skills (60%) and health promotion (54%); in terms of training the most popular areas were communication skills (62%) and the theory and practice of health promotion (48%). Fewer than one third of the nurses who were engaged in health checks for elderly people or the provision of diabetes care, asthma care or advice about the human immunodeficiency virus (HIV) and the acquired immune deficiency syndrome (AIDS) held an appropriate qualification. CONCLUSION: Practice nurses in the region were engaged in a wide range of activities for which many have had little formal training; the majority wished to develop their role and undertake further training. If practice nurses are to play a key part in the development of primary care services they must be adequately prepared for their clinical and health promotion role.

Education, Nursing, Continuing↗
PubMed1993

Evidence for a new tumour suppressor locus (DBM) in human B-cell neoplasia telomeric to the retinoblastoma gene.

Roughly 25% of human B-cell chronic lymphocytic leukaemias (CLL) are characterized by a chromosomal lesion involving 13q14. This region contains the retinoblastoma gene (RB1). We have used a variety of techniques to determine whether RB1 or some other locus is the critical region in 11 cases of low grade B-cell malignancy (mainly CLL), all with deletions or translocations involving 13q14. In all cases, except the one with minimal disease, there was deletion or a structural lesion in the region of D13S25, with at least 4 cases showing homozygous disruption. We conclude that D13S25 lies close to a tumour suppressor locus whose inactivation contributes to the initiation or progression of low grade B-cell malignancy. This locus is located at least 530 kilobases telomeric to RB1.

Alleles↗
PubMed1993

Structural abnormalities of the X chromosome in non-Hodgkin's lymphoma.

It has recently been reported that additional X chromosomes occur in over 30% of B-cell non-Hodgkin's lymphomas (NHL), and that monosomy of the X chromosome occurs in 38% of female patients with T-cell leukaemia or lymphoma. These observations have suggested a possible role for the X chromosome in the evolution of NHL. We have now examined 280 cases of NHL, and have identified 19 examples of structurally altered X chromosomes in the malignant cells from 17 of these cases. These abnormalities were mainly characterized by either a translocation involving Xp22, or a translocation/deletion involving Xq28. The relevance of these observations is discussed with respect to other published reports, and together they suggest that lymphoma-associated oncogenes may exist on the X chromosome at bands p22 or q28.

Aneuploidy↗
PubMed1991

Karyotypic abnormalities and immunoglobulin gene rearrangements in Hodgkin's disease.

Biopsy samples from seven patients with Hodgkin's disease (HD) were examined for cytogenetic abnormalities and rearrangement of the genes encoding the immunoglobulin chains and T-cell receptor chains. Three samples demonstrated clonal rearrangements of both IgH and IgL genes. No rearrangements of the TCR beta genes were detected in any of the samples. Karyotypic abnormalities were also found but only in the three cases where a clonal rearrangement of the immunoglobulin genes was shown. Two of these three cases had multiple karyotypic abnormalities, with the remaining patient being trisomic for chromosome 16 as the sole abnormality. These results are discussed and compared with previous reports in the literature concerning HD.

Adolescent↗