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Biomedical subjects

J Lyons

Publications and source records attributed to J Lyons.

At least 73 records · Page 4Linked to original sources
PubMed1989

Phase and amplitude analysis of exercise digital left ventriculograms in patients with coronary disease.

Phase and amplitude analysis was applied to intravenous digital left ventriculograms to avoid the artefacts associated with image subtraction. Eight controls and 40 patients with known coronary artery disease underwent digital left ventriculography before and after a symptom limited supine bicycle exercise test. The resultant images were subjected to phase and amplitude analyses. In the control group there was no deterioration in left ventricular wall motion after exercise. In 30 of the 40 patients there was a deterioration in wall motion on exercise. This group contained all eight patients with three vessel disease and 12 of the 17 patients with two vessel disease. Ten patients showed no change in wall motion--five with one vessel disease and five with two vessel disease. Phase and amplitude analysis of digital left ventriculograms is a method of detecting exercise induced myocardial ischaemia that may help in the assessment of patients with coronary artery disease.

Coronary Disease↗
PubMed1989

Clonal analysis of myelodysplastic syndromes: evidence of multipotent stem cell origin.

Restriction fragment length polymorphisms (RFLPs) of the X-chromosome genes hypoxanthine phosphoribosyl transferase (HPRT) and phosphoglycerate kinase (PGK) were studied in 34 female patients with primary myelodysplastic syndromes (MDS). Twelve patients (35%) were heterozygous at the HPRT or PGK loci for BamHI or BglI RFLPs, respectively. In eight patients showing PGK polymorphisms, clonality was determined by X-chromosome inactivation analysis. These included patients from different morphologic subtypes: four with refractory anemia (RA), two with RA and ring sideroblasts (RARS), one patient with RA with excess of blasts (RAEB), and one with chronic myelomonocytic leukemia (CMML). A monoclonal pattern of X-chromosome inactivation was observed in seven cases. In a further case characterized by bone marrow hypoplasia, peripheral blood (PB) leukocytes were polyclonal in origin. Following low-dose cytarabine therapy, reversion to polyclonal hematopoiesis was observed in a case of RAEB indicating the presence of residual normal hematopoietic stem cells with the capacity for marrow reconstitution. The clonal relation of lymphoid and granulocyte/monocyte lineages was studied directly in two cases of CMML exhibiting somatic mutations of N-ras or Ki-ras oncogenes. By selective oligonucleotide hybridization to ras gene sequences amplified in vitro by the polymerase chain reaction, a mutated ras allele was demonstrated in PB granulocytes, monocytes, and B and T lymphocytes of both patients. We conclude that MDS arise from a multipotent hematopoietic stem cell with the potential for myeloid and lymphoid differentiation.

Adult↗
PubMed1989

Acute myeloid leukemia: analysis of ras gene mutations and clonality defined by polymorphic X-linked loci.

In vitro DNA amplification and synthetic oligonucleotide hybridization was used to analyze 57 acute myelocytic leukemias (AML) for the presence of ras gene mutations. We demonstrated mutated alleles in 19% of primary AMLs (10/51) as well as in five of six secondary leukemias. Mutations occurred predominantly at N-ras codons 12, 13, or 61 (13 cases) and twice at Ki-ras codons 12 and 13. Ras gene mutations were preferentially associated with an M4 morphology according to the FAB (French-American-British) classification, but no particular correlation was observed with respect to clinical parameter (sex, age, course of disease) or immunophenotype and karyotype. Mutated ras alleles were absent in nine mutation-positive cases analyzed during remission. However, a more complex pattern emerged from the five patients analyzed in relapse exhibiting identical ras mutations in three cases, absence of a mutated allele in one patient, and acquisition of a N-ras mutation in yet another case, in which no mutation had been detected initially. Moreover, restriction fragment length polymorphisms (RFLP) of the X-chromosome genes hypoxanthine phosphoribosyl transferase (HPRT) and phosphoglycerate kinase (PGK) were studied in 19 of the AML patients. Nine cases (47%) were heterozygous for BglI or BamHI RFLPs at the PGK or HPRT loci, respectively, and therefore suitable for clonal analysis investigating X-chromosome inactivation. All of the patients exhibited a monoclonal leukemic cell population at presentation. In addition, five of seven cases studied in remission showed reemergence of a polyclonal pattern. However, two children exhibited persistence of monoclonal hematopoiesis despite complete clinical/hematological remission and a corresponding loss of a mutated ras allele in one of the patients. These data indicate the value of molecular genetic approaches for evaluation of the heterogeneous nature of remission and relapse in AML.

Adolescent↗
PubMed1988

Point mutation of the ras protooncogenes and chromosome aberrations in acute nonlymphocytic leukemia and preleukemia related to therapy with alkylating agents.

Nine cases of overt acute nonlymphocytic leukemia and four cases of preleukemia or a myelodysplastic syndrome, all related to intensive treatment with alkylating agents, were studied cytogenetically and investigated using a rapid and sensitive dot blot screening procedure for point mutations in the Ha-ras, Ki-ras, and N-ras protooncogenes within codons 12, 13, and 61. The technique involves a selective amplification of genomic DNA sequences containing the codon sequence of interest, in combination with oligonucleotide hybridization. Examining fractionated mononuclear cells from bone marrow or peripheral blood, an N-ras mutation at position 13 was observed in one patient with overt leukemia, resulting in a base change from GGT to TGT thus converting glycine to cysteine. The other cases exhibited no ras gene mutations. It is surprising that c-ras mutations are only occasionally observed in overt acute nonlymphocytic leukemia related to treatment with alkylating agents, as such abnormalities have often been observed in acute nonlymphocytic leukemia de novo, and as many alkylating agents are known to produce DNA adducts leading to point mutations and substitution of single amino acids. The fact that deletions of varying parts of the long arms of chromosomes 5 and 7 are observed in most cases of therapy-related acute nonlymphocytic leukemia and preleukemia, as confirmed by our own series of 71 patients, suggests that loss of heterozygosity for specific alleles on the two chromosomes, rather than activation of a protooncogene, could be an important step in leukemogenesis.

Acute Disease↗
PubMed1988

Incidence of ras gene mutations in neuroblastoma.

Using a rapid dot-blot screening procedure based on DNA amplification and hybridization to synthetic oligonucleotide probes, we investigated 18 neuroblastomas in various clinical stages for the presence of ras mutations. In none of the samples was a mutation in the relevant codons 12, 13 or 61 of Ha-ras, Ki-ras or N-ras found. These data virtually exclude the participation of mutated ras genes in the genesis of neuroblastoma.

DNA Mutational Analysis↗
PubMed1988

The social behavior of peer-identified aggressive, withdrawn, and aggressive/withdrawn children.

The behavioral patterns associated with peer ratings of aggression and withdrawal were explored. First, a discriminant function analysis (N = 74) using seven observational variables was found to significantly identify groups of Aggressive, Withdrawn, and Contrast fourth- and fifth-grade girls and boys. Aggressive/Withdrawn children were not distinguishable from Contrasts. In subsequent analyses comparing the behaviors of children in the four groups at two schools (total N = 117), children in the Aggressive and Withdrawn groups each showed distinctive patterns of social behavior, which were consistent across the two schools. The behavior of the Aggressive/Withdrawn children was not significantly different from that of Contrast children. However, results from one school suggested that Aggressive/Withdrawn children may receive a disproportionate amount of aggression from peers. Finally, the behavior patterns displayed by the deviant groups were similar for girls and boys, allowing for sex differences in base rates of playground behavior. These results confirm the observability of peer-identified patterns of aggression and withdrawal, and provide a detailed description of the behavior of such children in a free-play situation.

Aggression↗
PubMed1988

Rapid and non-radioactive prenatal diagnosis of beta thalassaemia and sickle cell disease: application of the polymerase chain reaction (PCR).

The standard method for the prenatal diagnosis of the haemoglobinopathies is by restriction enzyme mapping of chorionic villus DNA using Southern blotting and radioactively labelled gene probes. An improvement of the procedure which involves the selective amplification of DNA fragments by the polymerase chain reaction allows one to visualize restriction fragments directly without the use of radioactivity and within 2 d after obtaining the sample. We report here the prenatal diagnosis of two pregnancies at risk for homozygous beta thalassaemia and homozygous sickle cell disease using this novel approach.

Anemia, Sickle Cell↗
PubMed1988

Arrival-time analysis of intravenous digital aortograms in aortic dissection.

Arrival-time analysis was applied to intravenous digital aortograms. A single static image was produced by representing the time to 90% maximum density for each image pixel on a grey scale. Arrival-time analysis confirmed the diagnosis in four of six patients with aortic dissection that had been shown by image subtraction. In a further three patients with no dissection the arrival-time images were normal. In two patients with surgical repair of the ascending aorta, residual false lumens were shown by both subtraction and arrival-time analysis. In one of these cases arrival-time analysis prompted reanalysis of the subtraction image that had previously been interpreted as showing a normal aorta. Arrival-time analysis provides a static image of aortic dissection, which helps to overcome subtraction artefact.

Aortic Dissection↗
PubMed1988

Evidence for pluripotent stem cell origin of idiopathic myelofibrosis: clonal analysis of a case characterized by a N-ras gene mutation.

Three cases of idiopathic myelofibrosis were screened for the presence of mutations at codon 12, 13, or 61 of the ras gene family by a rapid method based on polymerase chain reaction and hybridization to mutation-specific oligonucleotides. PB cells of one patient showed a point mutation at codon 12 of the N-ras oncogene. This molecular genetic hallmark was used to investigate the clonal relationship of different cell lineages by cell separation analysis. Presence of the N-ras 12 mutation in granulocytes, monocytes, B cells, and T lymphocytes, as well as erythroblasts, indicates that idiopathic myelofibrosis originates from a pluripotent stem cell, at least in this patient.

Clone Cells↗
PubMed1988

Mutation of Ki-ras and N-ras oncogenes in myelodysplastic syndromes.

Somatic mutation of the N-ras oncogene occurs frequently in de novo acute myeloid leukemia (AML). By virtue of their relation to AML, myelodysplastic syndromes (MDS) provide an in vivo model of human leukemogenesis. By using a strategy for analysis of gene mutation based on in vitro amplification of target sequences by the polymerase chain reaction (PCR) and selective oligonucleotide hybridization we analyzed the mutational status of codons 12, 13, and 61 of Ha-ras, K-ras, and N-ras in peripheral blood (PB) and/or bone marrow (BM) in 34 cases of primary MDS. Mutations at codon 12 of Ki-ras or N-ras were detected in three cases (9%): one of six cases of refractory anemia with excess blasts (RAEB) and two of nine cases of chronic myelomonocytic leukemia (CMML). The nucleotide substitution differed in each. In all cases the mutant allele was detectable in PB cells. A sustained hematologic remission was achieved after low-dose cytarabine therapy in the case of RAEB. Neither case of CMML exhibited signs of disease progression during follow-up at 7 and 12 months. In contrast, four of 31 patients without the ras mutation underwent transformation to AML within 12 months of genetic analysis. We conclude that ras mutations in MDS are heterogeneous and may develop at an early stage during the evolution of MDS. Their detection in PB cells illustrates the potential utility of ras mutation as a clonal marker in myeloid malignancy.

Genes, ras↗
PubMed1988

Patients with heart rhythm disturbances: variables associated with increased psychologic distress.

The spectrum of psychologic distress in patients with serious heart rhythm disturbances (HRD) has not been well defined. A survey of personal and clinical background data and general psychologic status was made of 136 patients with serious HRD defined as sustained or symptomatic ventricular tachycardia or fibrillation. Two questionnaires were used: the SCL-90-R, a standard self-report symptom inventory of present psychologic status, and a functional capacity and occupational status questionnaire developed by us. Of the 105 respondents, 89 completed both questionnaires, the results of which form the basis of this report. The patients with HRD were found to have significantly elevated SCL-90-R scores reflective of an increase in overall psychologic distress (Global Severity Index, Positive Symptom Distress Index, and Positive Symptom Total) as well as significantly higher scores on the specific constructs. Within the HRD population, univariate analysis revealed three variables significantly correlated with increased psychologic distress: (1) requiring long-term antiarrhythmic medication, (2) being forced to modify work status, and (3) having more advanced cardiac impairment. Patients who had two or more of these variables, termed risk factors, reported significantly more symptoms and greater psychologic distress than those with zero or one risk factor. We conclude that patients with serious HRD have greater psychologic distress than do normal subjects. Within the HRD group, patients requiring long-term medical treatment for their arrhythmia, those forced to modify work status, and those with more advanced cardiac impairment are at greater risk for emotional sequelae, and patients with two or more of the identified risk factors are more likely to have elevated psychologic distress.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Concurrent mutations in two different ras genes in acute myelocytic leukemias.

DNA transfection analyses (tumorigenicity assay) and hybridization to mutation specific oligonucleotide probes established point mutations in codon 61 of both, N-ras and Ki-ras genes in fresh leukemic cells of an AML patient. Concurrent activation of N-ras and Ki-ras sequences by point mutations in codons 12 were demonstrated for AML cell line Rc2a. Moreover, using a rapid and sensitive dot-blot screening procedure based on the combination of in vitro amplification of ras specific sequences and oligonucleotide hybridization we could show that ras gene activation was not present in primary leukemic cells of the patient this cell line had been derived from, but rather occurred during later passages of Rc2a.

Animals↗
PubMed1987

RAS gene mutations in acute and chronic myelocytic leukemias, chronic myeloproliferative disorders, and myelodysplastic syndromes.

We report on investigations aimed at detecting mutated RAS genes in a variety of preleukemic disorders and leukemias of myeloid origin. DNA transfection analyses (tumorigenicity assay) and hybridization to mutation-specific oligonucleotide probes established NRAS mutations in codon 12 or 61 of 4/9 acute myelocytic leukemias (AML) and three AML lines. Leukemic cells of another AML patient showed HRAS gene activation. By using a rapid and sensitive dot-blot screening procedure based on the combination of in vitro amplification of RAS-specific sequences and oligonucleotide hybridization we additionally screened 15 myelodysplastic syndromes, 26 Philadelphia chromosome-positive chronic myelocytic leukemias in chronic or acute phase, and 19 other chronic myeloproliferative disorders. A mutation within NRAS codon 12 could thus be demonstrated in a patient with idiopathic myelofibrosis and in another with chronic myelomonocytic leukemia. Moreover, mutated NRAS sequences were detected in lymphocytes, in granulocytes, as well as in monocytes/macrophages of the latter case.

DNA, Neoplasm↗
PubMed1987

Intravenous digital subtraction angiography in the diagnosis and management of acute aortic dissection.

Eleven patients presenting with the clinical diagnosis of suspected aortic dissection underwent intravenous digital subtraction aortography. In nine patients digital subtraction angiography (DSA) was performed as the investigation of first choice. In five of these the diagnosis was confirmed with this technique alone and surgical repair was undertaken without further investigation. Direct cine aortography was also undertaken in the other four patients and confirmed the DSA findings, demonstrating aortic dissection in one case and no dissection in three others. In two of the eleven patients, direct cine aortography was performed as the initial investigation. The results of subsequent digital aortography concurred in both cases, aortic dissection being demonstrated in one patient. In two cases, despite normal cine and digital aortography, aortic dissection was confirmed by computed tomography. We have found DSA to be a valuable technique for diagnosing aortic dissection, with no false positive or false negative findings when compared to direct cine aortography. Since it is a less traumatic procedure than direct aortography it should be the investigation of choice if computed tomography is not immediately available.

Aortic Dissection↗
PubMed1987

What proportion of patients with myocardial infarction are suitable for thrombolysis?

Four hundred and three patients were considered for entry into a trial of intravenous streptokinase in suspected myocardial infarction. Three hundred and sixty seven (91%) were excluded. Two hundred and sixty (65%) did not meet the inclusion criteria and 45 of the remaining 143 (35%) patients had contraindications to thrombolysis. This left 98 (24%) patients who were suitable for thrombolysis and 42 of them were over 70 years, the upper age limit. Thus according to this trial protocol 56 (14%) patients were eligible for recruitment; 36 (9%) patients were finally randomised. These data suggest that treatment with intravenous streptokinase may be applicable to only a small proportion of patients with myocardial infarction.

Adult↗