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D Bevan

Publications and source records attributed to D Bevan.

31 records · Page 2Linked to original sources
PubMed1989

Alteration of the mechanical properties of sickle cells by repetitive deoxygenation: role of calcium and the effects of calcium blockers.

The formation of dense, poorly deformable sickle cells was studied by subjecting pre-separated, less dense cells to repeated deoxygenation and reoxygenation for 15 h. In the presence of Ca (2 mmol/l), this process caused the number of irreversible sickled cells to increase five-fold, mean cell haemoglobin concentration to increase by 13% and cellular potassium to decrease by 22%. Also, red cell filterability through 5 microns filter pores was greatly worsened. These effects decreased but were not totally abolished when the extracellular Ca concentration was lowered to zero or 0.01 mmol/l. If a high K medium was used (135 mmol/l), cell swelling rather than shrinkage occurred. Swelling also occurred if ouabain was added to the incubation. The Ca-channel blockers nitrendipine and nisoldipine had different effects. Nitrendipine, in the range 10(-7) - 10(-5) mol/l, was partially protective against all the induced changes, but nisoldipine was not protective at 10(-8) or 10(-6) mol/l. Thus, deterioration in the properties of sickle cells appears to be linked to Ca-dependent potassium loss during repeated sickling and is inhibited by nitrendipine.

Anemia, Sickle Cell↗
PubMed1988

The correlation of breakpoint cluster region rearrangement and p210 phl/abl expression with morphological analysis of Ph-negative chronic myeloid leukemia and other myeloproliferative diseases.

The chromosome 22 derivative, the Philadelphia (Ph) chromosome, results from a reciprocal translocation t(9;22) (q34;q11) and is associated with chronic myeloid leukemia (CML). The translocation can be identified at the DNA level in Ph-positive CML by using a probe to the breakpoint cluster region (bcr). In addition, as a result of this translocation an abl-related 210-kd protein with protein tyrosine kinase (PTK) activity is produced. We analyzed 28 cases of Ph-negative CML for rearrangement of the chromosome 22 sequences and found that eight of the 28 show rearrangement of the bcr. When 12 of the Ph-negative cases were independently reviewed, five were indistinguishable from Ph-positive CML on the basis of morphology, peripheral blood film and clinical details. These five also showed bcr rearrangement. The other seven were reclassified as six atypical CML (aCML) and one chronic myelomonocytic leukemia (CMML). None of these seven showed bcr rearrangement. In addition 11 cases of bcr- CML were assayed for abl-related PTK, and no detectable activity was present, whereas p210 phl/abl PTK was observed both in Ph-positive (three cases examined) and Ph-negative, bcr + (four cases examined) CML. Therefore, bcr + CML, whether or not the Ph chromosome is cytogenetically apparent, involves a similar molecular alteration and produces the 210-kd protein with enhanced PTK activity. Furthermore, these cases can be distinguished from Ph-negative bcr- CML by careful evaluation of clinical and hematologic data.

Chromosomes, Human, Pair 22↗
PubMed1987

Direct effect of interleukin 2 on chronic lymphocytic leukaemia B cell functions and morphology.

The functional and morphological changes induced by recombinant interleukin 2 (IL-2) were studied in purified B cells from patients with untreated B chronic lymphocytic leukaemia (B-CLL). In eight of nine patients, purified B-CLL cells increased their DNA synthesis in response to IL-2 without preactivation in vitro. This response, studied in detail in three patients, was dose dependent and reached a maximum on day 5 or 6. IL-2 induced or increased IgM secretion in cultures from five of the nine patients studied. Two of this responsive group were particularly interesting as IL-2 not only stimulated IgM secretion but also induced the secretion of IgG. Immunoglobulin production was invariably monoclonal. B CLL cells incubated with IL-2 showed distinct morphological changes including an increase in the size of cytoplasm and enlargement of nuclei together with the appearance of nucleoli. These changes were present in all IL-2 treated cultures but were more pronounced in those containing immunoglobulin secreting cells. None of the IL-2 induced changes appeared to correlate with the clinical stage of the disease or the level of Tac antigen expression on the freshly isolated CLL B cells.

Aged↗
PubMed1985

Monosomy 7 and multipotential stem cell transformation.

Monosomy 7 was the sole karyotypic abnormality seen in a case of biphenotypic leukaemia involving both the myeloid and lymphoid lineages and in a case of de novo ALL undergoing a phenotypic shift to acute myeloid leukaemia at relapse. These observations suggest that monosomy 7 can be associated with transformation of a common lymphoid-myeloid progenitor cell.

Aged↗
PubMed1983

Terminal deoxynucleotidyl transferase in acute myeloid leukaemia.

Between January 1980 and May 1981, 1966 marrow or blood samples from leukaemia patients were tested for terminal deoxynucleotidyl transferase (TdT) using nuclear immunofluorescence. The cells were also tested with a panel of immunological markers including monoclonal antibodies. Of 869 TdT positive cases detected, 555 were diagnosed as ALL and 32 as blast crisis of CGL; 226 were provisionally diagnosed as 'acute leukaemia' and finally diagnosed as ALL partly on the basis of immunological data; 56 TdT+ cases were provisionally diagnosed as acute non-lymphocytic or myeloid leukaemia; 266 cases of AML and 177 cases of CGL in blast crisis were TdT negative. Eleven of the above 'AML' cases were anti-cALL+ as well as TdT+ and were re-diagnosed and treated successfully as cALL. The remaining 45 were anti-cALL negative and finally diagnosed and treated, at least initially, as AML. Eleven of these cases had only 5-10% TdT+ cells which could have been normal, non-myeloid cells. Twenty cases had 11-50% TdT+ cells and 14 cases had 50-100% TdT+ cells. Of these latter two groups, details on 28 patients were available for evaluation. Three cases on review had no definitive myeloid cytochemistry and were haematologically AUL with a null-ALL phenotype (TdT+ DR+ cALL-). In 14 cases there was a large overlap (greater than 75%) of the proportion of cells with myeloid cytochemistry (Sudan black, peroxidase or esterases) and TdT; individual blast cells were therefore expressing these markers concurrently. In the remaining cases, mixtures of TdT negative myeloid and TdT+ (lymphoid?) cells may have coexisted although this was not proven unequivocally. Twenty-two cases of newly diagnosed TdT+ 'AML' received induction chemotherapy for AML (DAT regime) and only six (37%) obtained a complete remission. It is concluded that TdT positive 'myeloid' leukaemias do occur, albeit infrequently (approx. 5%) and may have a relatively poor prognosis.

Adolescent↗
PubMed1982

Leukaemia of platelet precursors: diverse features in four cases.

Four patients are described with malignant cells of definite or probable megakaryocytic lineage in the bone marrow and blood. Megakaryocytic features were defined by morphological and cytochemical studies using light and electron microscopy, and in two cases by reaction with a monoclonal anti-platelet antibody, AN51. All patients had increased bone-marrow reticulin, which developed in less than 15 months in two cases. One of these fitted the clinical pattern of acute myelosclerosis of Lewis and Szur (now widely referred to as acute megakaryoblastic leukaemia). Three cases had unique clinical features which are described in detail. There may be several variants of megakaryocytic leukaemia, including chronic forms. One variant is associated with Down's syndrome (trisomy 21).

Adult↗
PubMedDate not supplied

Immunoglobulin gene polymerase chain reaction to distinguish hyperreactive malarial splenomegaly from 'African' chronic lymphocytic leukaemia and splenic lymphoma.

Hyperreactive malarial splenomegaly (HMS) is found in geographical association with B cell lymphoproliferative disorders such as 'African' chronic lymphocytic leukaemia (CLL) and splenic lymphoma with villous lymphocytes (SLVL). It is sometimes not easy to make a differential clinical diagnosis between these conditions. We have previously used Southern blotting as a definitive method for the diagnosis of monoclonal lymphoproliferation in these disorders, but this is expensive, lengthy and technically difficult. In the present paper we have compared Southern blotting with polymerase chain reaction (PCR) amplification of the immunoglobulin heavy chain gene. We found an excellent correlation between the 2 methods in demonstrating monoclonal populations of lymphocytes in patients with a clinical diagnosis of CLL or SLVL. We have further demonstrated monoclonality in a patient who could not be classified as CLL or SLVL on clinical criteria alone. In contrast, patients with well defined HMS or with non-B cell proliferations all showed polyclonal rearrangements. We propose that the immunoglobulin gene PCR is a useful tool for the investigation of tropical splenomegaly of uncertain origin.

Adult↗
PubMedDate not supplied

Protein C deficiency associated with massive cerebral thrombosis following open heart surgery.

We describe a case of massive cerebral venous thrombosis following open heart surgery in a patient with a reduced level of Protein C (40% of mean level). Protein C deficiency is an inherited disorder which in the homozygous form may result in massive fatal venous thrombosis in the newborn. A Protein C level below 55% is highly suggestive of heterozygous deficiency and has been associated with a tendency to venous thrombosis although its clinical penetrance is variable. This is the first reported case of massive venous thrombosis in a patient following open heart surgery associated with Protein C deficiency.

Aged↗