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Biomedical subjects

A Jacobs

Publications and source records attributed to A Jacobs.

At least 217 records · Page 12Linked to original sources
PubMed1987

Effect of 13-cis-retinoic acid on survival of patients with myelodysplastic syndrome.

A randomised therapeutic trial of 13-cis-retinoic acid was carried out in 70 patients with myelodysplastic syndrome having 5% or fewer marrow blast cells. Among non-sideroblastic patients the 1-year survival in the treated group was 77%, compared with 36% in the control group. There were too few deaths among patients with sideroblastic anaemia to allow any effect of therapy on survival to be evaluated.

Adult↗
PubMed1987

The response of intracellular and surface ferritin after T-cell stimulation in vitro.

1. Measurements of T-lymphocyte surface ferritin using flow cytometry show that phytohaemagglutinin (PHA) stimulation causes a marked increase in the number of cells bearing spleen-type (S) and heart-type (H) ferritin on their membrane, whereas no such change occurs in non-stimulated cells. This coincides with increases in interleukin-2 receptors, transferrin receptors and HLA-DR antigen. 2. There is an increase in the intracellular concentration of both S- and H-ferritin in lymphocytes after PHA stimulation: H-ferritin increases five- to seven-fold, but S-ferritin only two-to three-fold. The maximum H/S ratio is about 15/1. However, these increases also occur in cells cultured in the absence of PHA. 3. Small amounts of both S- and H-ferritin are released into the medium, especially from stimulated cells, but the H/S ratios are lower than intracellular ratios. 4. The present findings suggest that lymphocyte stimulation followed by ferritin synthesis is accompanied by an increase in the amount of intracellular and cell surface ferritin and, possibly, the amount released from the cells.

Antigens, Surface↗
PubMed1987

Nuclear c-myc protein, maturation, and cell-cycle status of human haemopoietic cells.

Human c-myc protein, p62c-myc, has been quantitated by flow cytometry in the nuclei of normal marrow and peripheral blood cells, and the HL60 cell line. Marrow and peripheral blood cells exhibit nuclear c-myc protein throughout the cell-cycle, at an average level 2-3-fold lower than HL60 cells. In no cells did p62c-myc vary more than 2-fold throughout the cell cycle. A small subset of marrow G0/G1 cells, enriched in early myeloid and blast cell fractions, contained p62c-myc at levels equal to or even exceeding those of HL60. Overall c-myc protein content was higher in myeloid, compared to erythroid and lymphoid marrow fractions. Within the myeloid lineage, the highest average p62c-myc level was present in cells of intermediate maturation, i.e. myelocytes and metamyelocytes. In the erythroid lineage, c-myc protein level was highest in the most immature cells and declined with maturation. Significant amounts of p62c-myc were present in post-mitotic, end-stage neutrophils, but were barely detectable in cycling late erythroblasts or in quiescent lymphocytes and monocytes. HL60 cells, despite c-myc gene amplification and increased gene expression, contain c-myc protein at a level corresponding to promyelocytes in normal human marrow. The virtual absence of p62c-myc in cycling late erythroblasts, and its presence in post-mitotic end-stage granulocytes, suggests that c-myc protein may have functions unrelated to cell proliferation.

Bone Marrow Cells↗
PubMed1987

A randomized trial of 13-cis retinoic acid with or without cytosine arabinoside in patients with the myelodysplastic syndrome.

Ninety-eight consecutive patients with myelodysplastic syndrome were randomized to a treated or a control group, both receiving conventional supportive therapy. The treated group were given 13-cis-retinoic acid 20 mg/d if marrow blasts were less than or equal to 5% or cytosine arabinoside 10 mg/d subcutaneously on 6 d/week if marrow blasts were 6-30%, to which retinoic acid was added after 12 weeks. Serum levels of the drugs in the treated group were similar to those that would produce inhibition of CFU-GM growth in vitro. In patients in the low blast group receiving retinoic acid, myeloid surface antigens reverted from an abnormal to a normal pattern. Log rank analysis carried out after 25 months showed no significant difference in survival between the treated and control group, either in the total patient population or in the high and low blast groups considered separately. However, analysis of 39 non-sideroblastic patients with less than or equal to 5% blasts showed an increase in survival in the treated group.

Adult↗
PubMed1987

The effect of cytosine arabinoside on CFU-GM from patients with myelodysplastic syndrome.

CFU-GM clonal growth was examined in bone marrow from patients with myelodysplastic syndrome (MDS) in the presence of Ara-C at 10(-8) M and 4 X 10(-8) M and the response compared to the effect on progenitors from normal subjects. Seventy-three percent of marrow cultures from patients with MDS showed colony growth below the 95% confidence limits for normal subjects in the presence of 10(-8) M Ara-C. At 4 X 10(-8) M Ara-C 43% of marrow cultures had subnormal colony growth. These results suggest that CFU-GM from patients with MDS may have a greater than normal sensitivity to Ara-C.

Bone Marrow Cells↗
PubMed1987

Reduced in vitro erythroid progenitor cell growth in bronchial cancer.

Peripheral blood and bone marrow were studied in 21 men with disseminated untreated bronchial cancer in an attempt to define abnormalities of erythropoiesis associated with the development of anaemia. Haemoglobin concentration at or below 13 g/dl was present in 13 cases. Marrow morphology was normal in all cases except one, in which small numbers of tumour cells were found. Clonal assay of erythroid progenitors showed a significant decrease in the number of BFU-E (p = 0.03) and CFU-E (p = 0.01) compared with cultures from normal marrow (12 subjects). The growth of granulocyte and macrophage progenitors (GM-CFCs) was similar in patients with bronchial cancer and normal subjects. When normal marrow was incubated in the presence of serum from bronchial cancer patients, no inhibitory factors could be detected either for BFU-E or CFU-E growth. In all patients circulating T8 numbers were significantly raised (p = 0.0002). Consequently, the median T4:T8 ratio in blood was 1.2, and this was significantly lower than the ratio of 1.7 found in 20 normal subjects (p = 0.036). In 18 patients the bone marrow T4:T8 ratio of 1.1 was significantly lower than the ratio of 2.9 found in seven normal subjects (p = 0.04). Total blood white cell counts, neutrophils, and monocyte numbers were also increased (p = 0.0001; p = 0.0001; p = 0.002).

Aged↗
PubMed1987

Circulating micromegakaryocytes in myelodysplasia.

The alkaline phosphatase-antialkaline phosphatase (APAAP) immunocytochemical staining technique was used to look for circulating cells of megakaryocyte lineage in peripheral blood smears from 67 cases of myelodysplasia. Small numbers of micromegakaryocytes positive for platelet glycoprotein IIIa were found in 23 cases. These cells superficially resemble small lymphoid cells and are hence difficult or impossible to recognise in conventional Romanowsky stained smears. Circulating micromegakaryocytes were found most commonly in more aggressive types of myelodysplasia (such as refractory anaemia with excess blasts (RAEB) and refractory anaemia with excess blasts in transformation (RAEB-t], and their presence may therefore indicate a poor prognosis. Because of the simplicity of this immunocytochemical labelling technique, it could be of wide use in the initial assessment of patients with myelodysplasia, and possibly for the early detection of acute leukaemic transformation.

Adolescent↗
PubMed1987

Myeloid surface antigen abnormalities in myelodysplasia: relation to prognosis and modification by 13-cis retinoic acid.

The relation between prognosis and lineage specific surface antigen expression on peripheral blood granulocytes and monocytes was studied using monoclonal antibodies and flow cytometry in 37 patients with myelodysplastic syndromes (MDS). Abnormalities in antigen expression were summarised as a score, and cases were divided into low (few abnormalities) and high (many abnormalities) groups. Survival was significantly worse in the "high" group (logrank chi 2 = 5.793, p = 0.016), this group having a median survival of 31 weeks, compared with more than 67 weeks in the "low" group. No correlations were found between the score and any of the following: peripheral blood platelet and granulocyte count; FAB subtype; bone marrow blast cells and sideroblast count, or erythroid and myeloid progenitor growth. Antigen expression was also studied in six further cases of MDS before and after six weeks of treatment with 13-cis retinoic acid (CRA), 20 mg given orally, and a comparison was made with six untreated patients studied before and after a similar time interval. In the treated group 58% of initially abnormal measurements reverted to normal, compared with 24% in the untreated group. Five of the six treated patients showed a decrease in the score, whereas only two of the six improved in the untreated group. The data indicate that myeloid antigen expression is a useful indicator of prognosis in MDS, and that antigen expression may be affected by treatment.

Adult↗
PubMed1987

Haemoglobinopathy screening in a 'low-risk' area of the United Kingdom: South Glamorgan, Wales.

Figures collected over 2 1/2 years of screening of women attending the antenatal clinics of South Glamorgan, Wales, showed that the percentage of women identified as a risk for haemoglobinopathy trait (7.4%) was almost twice that estimated from the 1981 Census data (4.1%) and that the incidence of a thalassaemia trait in these women (0.38% beta; 0.68% alpha) was similar to that of an area of supposedly greater risk in London (0.46% beta; 0.42% alpha). Figures from one laboratory showed that without a scrutiny of all antenatal clinic blood counts for thalassaemic indices some thalassaemia traits will be missed. The apparent incidence of the HbS trait was 0.13%, and reasons for this being an underestimate are given.

Female↗
PubMed1987

Enrichment of progenitor cells from human marrow.

Suspensions enriched for myeloid and erythroid colony-forming cells were prepared from human marrow by simultaneous treatment of low-density cells with the monoclonal antibodies Campath-1 and 80H.3, followed by immune-rosetting; lymphocytes and monocytes were successfully removed by this method. The final suspension contained 22% of blasts and 70% primitive myeloid-monocytic cells. GM-CFCs, counted after 14 days of culture, were enriched 21-fold. Of all cells present in the final suspension, 10.8% were day 8 GM cluster-forming cells, 2.3% were day 8 GM colony-forming cells, 2.4% were day 7 CFU-E, 0.9% were day 14 GM cluster-forming cells, 1.1% were day 14 GM colony-forming cells, and 0.6% were day 14 BFU-E. After enrichment, BFU-E became markedly more dependent on the addition of 5637-conditioned medium as a source of growth factors, suggesting that lymphocytes and/or monocytes support erythroid progenitor growth in cultures of unfractionated marrow. By removing these cells, we obtained a sensitive assay for burst-promoting activities in conditioned media. This procedure can be used to study the roles of marrow lymphocytes and monocytes in hemopoiesis as well as providing a basis for the purification of normal and aberrant progenitors.

Bone Marrow Cells↗