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Biomedical subjects

D A Winfield

Publications and source records attributed to D A Winfield.

At least 37 records · Page 2Linked to original sources
PubMed1994

Comparison of protein synthesis profiles in chronic lymphocytic leukaemia cells and B-lymphocytes from peripheral blood, cord blood and tonsil.

2D-gel electrophoresis was used to investigate protein synthesis in leukaemic cells from a series of 15 chronic lymphocytic leukaemia (CLL) patients, and in non-malignant B-cell populations from different sources. The protein synthesis profiles of CD5+ B-cells from umbilical cord blood and from tonsil were determined, and the levels of expression of their proteins were observed to be similar to the CLL cells. The CD5- cells from cord blood resembled peripheral blood B-lymphocytes, and the protein synthesis profile of CD5- cells from tonsils was very complex. One protein was also identified which consistently appeared to be synthesised at a low level in CD5+ B-cells from tonsil but which was always more prominent in CLL cells and other non-malignant B-lymphocytes. On the basis of these data it is possible that the closest non-malignant counterpart to CLL is the CD5+ B-lymphocyte from cord blood.

Antigens, CD↗
PubMed1994

2D-gel analysis of protein synthesis profiles of different stages of chronic lymphocytic leukaemia.

Protein synthesis profiles of leukaemic cells from 15 chronic lymphocytic leukaemia (CLL) patients were analysed by 2D-electrophoresis of 35S-methionine labelled proteins. This series of CLL included patients with stage A (7), B (4) and C (4) disease. Although the protein synthesis profiles were similar in all cases, some consistent differences were noted between the different stages. The levels of synthesis of three proteins (approximately 35 kD size) were of particular interest. Two of these were always expressed in stage C CLL but either infrequently or not at all in stage A or B CLL. By contrast a third protein was expressed at a much reduced level in stage C compared to stages A or B. This type of analysis could prove invaluable for identifying proteins whose expression was intimately associated with the evolution of CLL.

Electrophoresis, Gel, Two-Dimensional↗
PubMed1993

2D-gel analysis of proteins in chronic lymphocytic leukemia cells and normal B-lymphocytes.

Protein synthesis was analysed in leukaemic cells from 10 chronic lymphocytic leukaemia (CLL) patients by 2D-gel electrophoresis of 14C-labelled proteins. There appeared to be only minor differences between each of the CLL samples, but there was evidence that the level of expression of a few of the proteins might have correlated to the stage of the disease. Comparison of the CLL samples to populations of normal B-lymphocytes demonstrated marked differences in protein synthesis between the leukaemic and non-malignant cells. We subsequently used the fluorescence activated cell sorter (FACs) to separate CD5+ from CD5- B-lymphocytes, but observed that the protein synthesis exhibited by these two populations was essentially the same, and both were very different to that observed in CLL cells. The significance of these observations with respect to the origins of CLL is discussed.

Antigens, CD↗
PubMed1993

Investigation of BCL-2 gene rearrangements in a United Kingdom series of low and high grade non-Hodgkin's lymphomas.

Rearrangements of the BCL-2 gene are thought to be the most frequent genetic changes that occur in non-Hodgkin's lymphomas (NHL), and are particularly associated with follicular low grade disease. Wide variations in the frequency of these rearrangements have, however, been reported in studies of NHL series from different parts of the world. We were therefore interested to determine the frequency of BCL-2 gene rearrangements in the different grades of NHL from a U.K. series. We have done this by using a combination of Southern blot hybridization and polymerase chain reaction (PCR) analysis. The frequencies of rearrangements in our series were 9/20 (45%) in low grade follicular NHL, 1/8 (12.5%) in low grade lymphocytic and 5/19 (26%) in high grade NHL. However, estimation of the high grade value was complicated by the fact that a number of the high grade samples in our series were from patients who had transformed from low grade follicular disease. If the patients were ranked on the basis of whether they had a history of low grade follicular disease then the frequency of BCL-2 rearrangement remained the same 13/29 (45%), but was only 1/10 (10%) in high grade NHL with no history of follicular disease. The former figure was intermediate between those reported for the USA and Japan series, but the latter high grade figure was the lowest reported from any series. The significance of BCL-2 rearrangements in the evolution of both low and high grade NHL is discussed.

Base Sequence↗
PubMed1992

Diagnosis of acute promyelocytic leukaemia by RT-PCR: detection of PML-RARA and RARA-PML fusion transcripts.

Acute promyelocytic leukaemia (APL; AML M3) is identified by a unique t(15;17) translocation which fuses the PML gene to the retinoic acid receptor alpha gene (RARA). Reverse transcription coupled with the polymerase chain reaction (RT-PCR) has been used to develop a diagnostic test for APL based on the PML-RARA fusion message. Separate PCR assays were designed to amplify either PML-RARA (15q+ derived) or RARA-PML (17q- derived) chimaeric transcripts. PML-RARA transcripts were detected in every case from a series of 18 APL patients with cytogenetically confirmed t(15;17) translocations, whereas RARA-PML messages were detected in only 67% (12/18) of these patients. This suggests that it is the 15q+ derivative which mediates leukaemogenesis. Furthermore the PCR approach (or Southern analysis) may be used to identify in which of the alternative PML introns the breakpoint occurs; 52% of cases (15/29 patients) utilize a 5' PML intron and 48% the 3' intron (14/29 cases). Neither the choice of PML intron nor the expression of the 17q- derivative could be correlated with the microgranular variant of APL (M3V), overall survival rate, age, sex or presence of coagulopathy. Finally, the fusion message is undetectable in five remission samples. This indicates a possible use for RT-PCR in monitoring remission patients for evidence of relapse.

Adolescent↗
PubMed1991

Bone marrow aplasia in B cell chronic lymphocytic leukaemia: successful treatment with antithymocyte globulin.

Pure red cell aplasia is a rare but well known association of chronic lymphocytic leukaemia (CLL). Pancytopenia due to bone marrow aplasia has not been previously described in CLL. A 42 year old man with B cell CLL became severely pancytopenic with bone marrow aplasia. Bone marrow culture resulted in a greatly reduced colony formation. High dose corticosteroids and intravenous immunoglobulin treatment were unsuccessful. Prompt and complete marrow recovery ensued after administration of antithymocyte globulin.

Adult↗
PubMed1991

Partial splenectomy for massive splenomegaly secondary to Gaucher's disease.

A 16 year old girl with Type 1 Gaucher's disease presented with massive splenomegaly, hypersplenism and abdominal discomfort. Traditionally hypersplenism has been treated with splenectomy, but this results in a high incidence of overwhelming sepsis and accelerated sphingolipid deposition in both liver and bone. A 90% partial splenectomy was therefore performed leaving a fully vascularized inferior segment of the spleen and resecting 5.8 kg of splenic tissue. The patient made an uneventful recovery with a marked improvement in her haematological parameters and general condition.

Adolescent↗
PubMed1991

The chest radiograph appearances seen following high dose chemotherapy and autologous bone marrow transplantation for resistant malignant lymphoma.

The objective of this study was to review and analyse the chest radiograph (CXR) appearances seen following high dose chemotherapy and autologous bone marrow transplantation (ABMT), and to identify any characteristic patterns. Thirty-one patients underwent ABMT between 1984 and 1989 for high grade lymphoma resistant to conventional chemotherapy. Their case notes and CXRs were reviewed in conjunction with the clinicians. In this small sample of patients, an acute interstitial pattern was seen with pulmonary oedema following bone marrow reinfusion in two cases of the 13 patients showing CXR changes (15%). Otherwise, the CXR changes following ABMT were not specific, although they did alert the clinician to the possibilities of recurrent lymphoma or opportunistic infection, enabling appropriate investigations and treatment to be instituted at an early stage. The complications and CXR changes did not differ greatly from those seen following allogeneic bone marrow transplantation.

Adolescent↗
PubMed1990

Mitoxantrone for refractory and relapsed acute leukemia.

Seventy-seven patients with relapsed or refractory acute leukemia and three with acute blastic chronic myeloid leukemia (CML) were treated in an open Phase II study using mitoxantrone 12 mg/m2 intravenously daily X 5 days. Complete remission (CR) was achieved in 32 of 80 (40%), including 23/45 (52%) with relapsed acute nonlymmphocytic leukemia (ANLL), four of 12 (33%) with relapsed acute lymphocytic leukemia ALL, four of 17 (24%) with ANLL refractory to daunorubicin + cytosine arabinoside, and one of three (33%) with refractory ALL. None of the patients with acute blastic CML achieved CR. Median survival time for all patients was 121 days. Median duration of complete response was 303 days with ten of 32 patients in continuing CR for periods varying from 44+ to 1210+ days. Apart from moderately prolonged hematologic suppression toxicity was mild and subjective side effects were tolerable. Mitoxantrone is an active agent in the treatment of acute leukemia and demonstrates incomplete cross resistance with duanorubicin. Mitoxantrone should be considered for first-line therapy in ANLL.

Drug Administration Schedule↗
PubMed1990

A comparative efficacy and safety study of teicoplanin plus aztreonam versus gentamicin plus piperacillin in haematology oncology patients with clinically diagnosed septicaemia.

Infections due to Gram-positive bacteria, especially coagulase-negative staphylococci, have been increasing in immunocompromised patients during the last 5 years because of an increased use of Hickman catheters and oral gut decontamination with quinolones. Teicoplanin, a new glycopeptide antibiotic, has a long plasma half-life which allows once-a-day bolus administration, making it a 'user friendly' agent. A randomized comparative evaluation of teicoplanin plus aztreonam versus gentamicin plus piperacillin in leukaemic patients with a clinical diagnosis of septicaemia was undertaken. The objectives of this study were (1) to evaluate the efficacy and safety of teicoplanin and aztreonam in comparison to a 'standard antibiotic' regimen and (2) to assess the local and systemic tolerance of these drugs. Results of the study in more than 70 patients to date are presented, and the role of anti-Gram-positive antibiotics in the management of severe sepsis in immunocompromised patients is discussed.

Adult↗
PubMed1990

Evans' syndrome associated with dermatomyositis.

Autoimmune haematological complications in dermatomyositis are very uncommon. This case report describes autoimmune haemolytic anaemia and thrombocytopenia in a patient with dermatomyositis and pulmonary fibrosis.

Aged↗
PubMed1989

Granuloma formation in herpes zoster scars.

An 82-year-old male with chronic lymphocytic leukaemia developed an erythematous papular eruption over the trunk. Lesions occurred at the site of scars related to a disseminated herpes zoster infection 3 months previously. Biopsy of a lesion showed granuloma formation. The rash resolved spontaneously over 6-8 weeks.

Aged↗