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Biomedical subjects

M Bower

Publications and source records attributed to M Bower.

At least 109 records · Page 6Linked to original sources
PubMed1994

Prevalence and clinical correlations of MLL gene rearrangements in AML-M4/5.

Rearrangements of the human trithorax gene (MLL, HRX, Htrx-1, All-1) were studied by Southern blotting in blast cells stored at presentation from 65 adults with de novo acute myelomonocytic (AML-M4) and acute monocytic leukemia (AML-M5). MLL rearrangements were demonstrated in 15 (23%) cases, including eight patients in whom karyotype analysis had failed to detect abnormalities of chromosome band 11q23. The patients with MLL rearrangements did not differ significantly from those with germline configurations in terms of the sex and age of the patients, the presence of lymphadenopathy, hepatosplenomegaly, or central nervous system involvement, and the absolute blast count at diagnosis. Kaplan-Meier analysis of the treated patients demonstrated no difference in survival for patients with MLL rearrangements compared with those without rearrangements. Therefore, in contrast to infantile acute leukemia, in adults with AML-M4 and AML-M5, MLL rearrangements do not identify a subgroup of patients with different clinical features or prognosis.

Adolescent↗
PubMed1994

Human trithorax gene rearrangements in therapy-related acute leukaemia after etoposide treatment.

Molecular analysis of leukaemic blasts from 9 patients with secondary myeloid leukaemia reveals rearrangements of the human trithorax gene (Htrx-1) in three patients, including one in whom abnormalities of chromosome 11 band q23 were not detected by conventional cytogenetics. All three patients had been treated with epipodophyllotoxins, whilst none of the six without rearrangements had received these agents. The patients with rearrangements also presented with different clinical features. These findings support the separation of secondary leukaemia into two classes, and correlate rearrangements of the Htrx-1 gene with a group of secondary leukaemias that follow specific cancer treatment regimens.

Adult↗
PubMed1993

Structure and expression of the human trithorax-like gene 1 involved in acute leukemias.

The human trithorax-like gene 1 (Htrx1 gene) is disrupted in 11q23 translocations that are associated with acute leukemias. Sequencing of a partial human cDNA revealed an open reading frame encoding 1012 amino acids with extensive homology to the Drosophila trithorax protein, particularly in the zinc finger-like domains. Htrx1 gene appears to be unique in the human genome and has been conserved during evolution. Use of the human cDNA as a probe demonstrates that this gene is interrupted in both infant and adult acute myeloid (AML) and lymphoid (ALL) leukemia patients with 11q23 translocations. The structure of the Htrx1 gene around the breakpoints shows that this part of the human gene is interrupted by nine introns. As a result of the rearrangement, zinc finger domains are translocated in both ALL and AML patients. Expression studies reveal that the Htrx1 gene differentially expresses three transcripts within the normal lymphocyte cell lineage.

Acute Disease↗
PubMed1993

In situ hybridisation analysis of a homogeneously staining region at 11q23-24 in an acute myeloid leukaemia (M5) using yeast artificial chromosomes.

An example of a homogeneously staining region (hsr), occurring in an acute myeloid leukaemia (M5) on chromosome 11 in the region of bands q23-q24, has been analysed. In situ hybridisation using yeast artificial chromosome (YAC) DNA demonstrated that the amplification did not include the CD3 gene cluster and did not affect the human trithorax gene known to be disrupted by translocations at 11q23. In contrast, the amplification was shown to include the sequence D11S543 which has been previously mapped to chromosome band 11q24. High resolution analysis using confocal microscopy allowed the individual amplicons to be visualised, and it was shown that the hsr consisted of an 8-fold amplification of the region surrounding the probe D11S543. From previous estimates of human chromosome size it was possible to calculate that the hsr was composed of amplicons approximately 10 megabases in length. It was concluded that the region amplified did not extend as far as the translocation breakpoints occurring at 11q23 in acute leukaemias.

Aged↗
PubMed1992

Chromosome 11q23 translocations in both infant and adult acute leukemias are detected by in situ hybridization with a yeast artificial chromosome.

The yeast artificial chromosome (YAC-13HH4), which spans a 440-kb region of DNA just distal to the CD3 locus on chromosome 11 at band q23, has been used to characterize a range of chromosomal translocations in acute leukemias from both adults and infants. In situ hybridization was performed on metaphase cells from bone marrow of 17 leukemias and two cell lines with a variety of chromosome 11q23 abnormalities. It was established that in infant leukemias the translocations t(11;19), t(4;11), and t(5;11) had occurred in the region defined by YAC 13HH4. Additionally, the translocations t(4;11), t(6;11), t(9;11), t(X;11), and t(10;11) in other leukemias were found to disrupt the same region of chromosome 11q23, although an exception was found in one t(6;11) translocation for which the breakpoint was distal to the YAC. One patient had a t(9;11) translocation in a therapy-related leukemia, suggesting that this class of etoposide-related malignancy has similar breakpoints to those occurring in de novo leukemias. An example of a lymphoma-derived translocation t(4;11) was shown to involve a deletion of the region defined by YAC 13HH4. A leukemia with a deletion on chromosome 11 (q23-q25) was also studied and it was shown that the YAC sequence was unaffected. It was concluded that, with a few exceptions, the translocations at 11q23 in a wide range of acute infant and adult leukemias occur in a common region and may result from a common underlying mechanism.

Acute Disease↗
PubMed1992

Molecular cloning and analysis of chromosome band 11q23 involved in leukaemia-associated translocations.

Three overlapping yeast artificial chromosomes (YACs) spanning a 780 kb region of DNA around the CD3 locus on chromosome 11 have been isolated and characterised. The individual cloned regions have been mapped by in situ hybridisation to chromosome band 11q23, and a restriction enzyme map of this region has been constructed. The positions of these clones in relation to a series of leukaemia-associated chromosomal translocations has also been determined. It was concluded that, although two clones lay entirely proximal to the breakpoints examined, the third clone (13HH4) encompassed the breakpoints for the translocations t(4;11), t(6;11), and t(9;11). The t(9;11) was observed in an acute myeloid leukaemia in a patient previously treated for an unrelated malignancy. It would thus appear that the breakpoints at chromosome band 11q23 occurring in therapy-related leukaemias are in the same region as those found in adult and childhood acute leukaemias and may result from a common underlying mechanism.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1992

A double-blind study of the efficacy of metronidazole gel in the treatment of malodorous fungating tumours.

A double-blind placebo-controlled trial was undertaken to assess the value of topical metronidazole gel preparation in the palliation of the offensive odour of fungating tumours. This 5 day trial was followed by a 6 day period during which all patients received the active gel. Subjective odour assessments were performed by both patients and medical staff. 11 patients were entered and the randomisation was then halted because of an obvious overall benefit over the whole 11 days. There was a non-significant trend in favour of the active treatment during the initial double-blind placebo-controlled phase of the trial, and no side-effects were observed.

Administration, Topical↗
PubMed1992

Mitozantrone and methotrexate chemotherapy with and without mitomycin C in the treatment of advanced breast cancer: a randomised clinical trial.

Patients with advanced breast cancer were randomised to 3M (mitozantrone 6.5 mg/m2q 21 days, methotrexate 30 mg/m2q 21 days, mitomycin C 6.5 mg/m2q 42 days) or 2M (as 3M but without mitomycin C). The objective response rates of 30% in 51 evaluable patients receiving 3M and 26% of 54 patients receiving 2M were not significantly different. 4/16 patients not responding to 2M responded to 3M on crossover. Both regimes were well tolerated but there was significantly less haematological toxicity and fewer dose reductions and delays with 2M. We conclude that patients should initially be treated with 2M and that non-responding patients should be crossed to 3M.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

A trithorax-like gene is interrupted by chromosome 11q23 translocations in acute leukaemias.

Some acute lymphocytic leukaemias, particularly those in young children, are associated with a t(4;11)(q21;q23) reciprocal translocation. We have cloned the translocation breakpoint on chromosome 11q23 and isolated corresponding RNA transcripts from this region. The translocation occurs within a cluster of Alu repetitive elements located within an intron of a gene that gives rise to 11.5 (kb) transcript spanning the translocation breakpoint. The 11.5 kb transcript encodes a protein that is highly homologous to the Drosophila trithorax gene, a developmental regulator. An analysis of a series of leukaemic patients carrying t(4;11) and t(9;11) translocations indicate that the majority of breakpoints in infant leukaemias lie within a 5 kb region.

Amino Acid Sequence↗
PubMed1991

Topical calcipotriol treatment in advanced breast cancer.

19 patients with locally advanced or cutaneous metastatic breast cancer were treated with the topical vitamin D analogue calcipotriol 100 micrograms daily. 14 patients completed 6 weeks' treatment; 3 showed a 50% reduction in the bidimensional diameter of treated lesions and 1 other patient showed a minimal response. 2 patients became hypercalcaemic during treatment. In all patients who responded the tumours contained receptors for 1,25-dihydroxyvitamin D3, shown by immunocytochemistry.

Administration, Topical↗
PubMed1990

The value of serum cryptococcal antigen in the diagnosis of cryptococcal infection in patients infected with the human immunodeficiency virus.

Serum cryptococcal antigen titres were measured in 828 HIV-infected patients with pyrexia, 69 of whom had meningism. Serum cryptococcal antigen was positive in 17 patients of whom 16 had meningism with cryptococcus isolated from their CSF. The other patient had no meningism, had no evidence of cryptococcal infection on repeated CSF examination and remains well. A positive serum cryptococcal antigen test was therefore valuable in the diagnosis of cryptococcal meningitis, although in all 16 patients meningism was present and a diagnostic lumbar puncture was therefore carried out. In our experience routine screening for serum cryptococcal antigen did not predict patients who subsequently developed cryptococcal meningitis.

Amphotericin B↗
PubMed1990

The significance of the detection of cytomegalovirus in the bronchoalveolar lavage fluid in AIDS patients with pneumonia.

We performed a retrospective study on 112 patients with AIDS-related pneumonias who underwent bronchoscopy and in whom Pneumocystis carinii pneumonia (PCP) and/or cytomegalovirus (CMV) were identified in bronchoalveolar fluid (BAL). CMV was identified by detection of early antigen fluorescent foci (DEAFF) testing in cell cultures of BAL fluid. The short- and long-term survival of all patients was similar regardless of whether PCP, CMV or both were detected at bronchoscopy. Ten out of 14 patients with CMV alone and 13 out of 26 with both CMV and PCP were treated with anti-CMV therapy, but the short- and long-term mortality was similar to that in patients who had no specific antiviral therapy. Extrapulmonary recurrence of CMV (retinitis or gastrointestinal disease) occurred in 22% of patients with evidence of CMV in BAL compared with 16% of those with PCP alone, but this difference was not statistically significant and this recurrence rate was independent of anti-CMV therapy. Detection of CMV shedding from more than one site (BAL, urine, throat or blood) was associated with a worse prognosis at 3 months than in patients in whom CMV was detected in BAL alone. It does not appear that finding CMV shedding is a guide to the cause of pneumonia or an indication for treatment in AIDS patients.

Acquired Immunodeficiency Syndrome↗