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Biomedical subjects

A Jacobs

Publications and source records attributed to A Jacobs.

At least 199 records · Page 11Linked to original sources
PubMed1989

Preleukaemia and myelodysplastic syndromes today.

The clinical picture of myelodysplastic syndromes (MDS) results from the expansion of an abnormal clone of haemopoietic stem cells that has undergone premalignant transformation. Different types of "oncogene" may be involved in this process, some of which code for growth factors and their receptors, some for membrane or cytoplasmic proteins and some for nuclear binding proteins. The insults causing gene mutations are not known, though chemical, viral or radiation damage could be important. The most striking feature of MDS is the inadequate production of dysplastic, poorly functional cells as a result of impaired differentiation and premature cell death in the bone marrow. Treatment is currently directed to supportive therapy with blood components and antibiotics, attempts to stimulate proliferation and differentiation with recombinant human growth factors, and, in a few cases, bone marrow transplantation. Chemotherapy alone has met with little success.

Humans↗
PubMed1989

Myelodysplasia, chemical exposure, and other environmental factors.

This paper describes a case-control study of the occupational and environmental exposures of patients with myelodysplasia. The methodology, first described in Canada for solid tumors, estimates lifetime exposures to a number of potential toxic hazards or carcinogens. This pilot study confirms that the methodology, with the use of questionnaires and interviews, can estimate exposures to specific chemicals and shows some significant associations with myelodysplasia, including exposure to petrol or diesel compounds.

Air Pollutants↗
PubMed1988

Undetectable peripheral blood CFU-GM as a prognostic indicator in myelodysplastic syndrome.

The survival of MDS patients without detectable circulating CFU-GM (median = 188 days) was significantly lower than those in whose peripheral blood CFU-GM were detected (median greater than 1000 days) (p less than 0.01). About half of those with detectable PB-CFU-GM died within 2 yr whilst the remainder survived more than ca 3 yr. There was no significant difference in the distribution of patients having 0-5% and greater than 5% marrow blast cells within the three groups.

Anemia, Refractory↗
PubMed1988

The Ha-ras polymorphism in myelodysplasia and acute myeloid leukaemia.

We have assessed the possibility that rare allelic variants of the c-Ha-ras-1 locus may be linked to a susceptibility to malignancy [1]. c-Ha-ras-1 genotypes were scored in 41 patients with myelodysplasia (MDS), 51 patients with acute myeloid leukaemia (AML) and 52 normal subjects. The incidence of rare alleles in the MDS patients was 4.8% and in AML an incidence of 15.7% was found. No rare alleles were found in the normal subjects. We conclude that rare alleles in MDS are not a common predisposing factor.

Alleles↗
PubMed1988

Ferritin-bearing T-lymphocytes and serum ferritin in patients with breast cancer.

Flow cytometric studies of T-lymphocytes in breast cancer patients show that the number of cells bearing ferritin on their surface is significantly greater than normal. The number of ferritin-bearing T-cells does not appear to be related to the clinical stage of the disease nor to the serum ferritin concentration, though this is higher in cancer patients than in normal women. There is no difference in the number of T-cells positive for interleukin 2 or transferrin receptors nor in the absolute number of T-cells, T-helper cells and B-cells between normal women and those with breast cancer or benign breast disease. However, there is a significant increase in the level of HLA DR-positive T-cells and T-suppressor cells in breast cancer patients. While the significance of ferritin-bearing T-cells is not known an increase in their number appears to be associated with cancer.

Adult↗
PubMed1988

Effect of phytohaemagglutinin on the synthesis and secretion of ferritin in peripheral blood lymphocytes.

Stimulation of lymphocytes with phytohaemagglutinin (PHA) causes an increase in the rate of ferritin and total protein synthesis which is not enhanced by supplementing the medium with iron. There is an increase in intracellular ferritin content which is amplified by the presence of iron but this is also observed in the absence of PHA stimulation. The increased cellular ferritin is greater for heart type ferritin than for spleen type ferritin. Ferritin secreted into the medium from the cells shows a relative preponderance of spleen type ferritin compared to the intracellular protein. The data shows a dissociation between ferritin synthesis, cellular accumulation and secretion for which the mechanisms have still to be elucidated.

Blood Proteins↗
PubMed1988

Enrichment of haemopoietic progenitor cells from the marrow of patients with myelodysplasia.

Myeloid and erythroid progenitors from myelodysplastic marrows have been separated from accessory cell populations likely to influence their in-vitro growth. Myeloid colony-forming cells were enriched 23-fold and erythroid progenitors 5-7-fold but, in both cases, retained their abnormal growth characteristics. After enrichment and removal of lymphocytes and monocytes, erythroid burst formation became markedly more dependent on the addition of 5637 bladder carcinoma conditioned medium as an exogenous source of haemopoietic growth factors. This suggests that lymphocytes and monocytes usually support erythropoiesis in cultures of myelodysplastic marrow and demonstrates that erythroid burst-forming progenitor cells from myelodysplastic patients can respond to these populations in vitro. Haemopoietic failure in myelodysplasia appears to result from a defect within the preleukaemic clonogenic cell, rather than from an aberration in exogenous factors. The procedure outlined here can be used as a first step towards the isolation of these abnormal progenitors.

Aged↗
PubMed1988

5-Aminolaevulinic acid synthase activity in developing human erythroblasts.

5-Aminolaevulinic acid (ALA) synthase activity was measured in highly purified preparations of age-matched human erythroblasts. Enzyme activity in immature normoblasts was four-fold higher than that found in late orthochromatic normoblasts. ALA synthase activity in the immature erythroblasts in primary acquired sideroblastic anaemia (PASA) was reduced and remained unchanged during further erythroid differentiation. The pattern of erythroblast ALA synthase activity in two patients with congenital dyserythropoietic anaemia (CDA) and in one patient with beta-thalassaemia intermedia was similar to that found in PASA. This study has clearly demonstrated reduced erythroblast ALA synthase activity in PASA but has also found reduced enzyme activity in conditions in which ring sideroblasts are not prominent. This would suggest that haem synthesis is abnormal in PASA but that reduced erythroblast ALA synthase activity does not inevitably lead to ring sideroblast formation.

5-Aminolevulinate Synthetase↗
PubMed1988

Myelodysplastic syndrome in a kindred with ins(16) (p11.2).

A constitutional karyotypic abnormality, ins(16)(p11.2), is described in a case of myelodysplastic syndrome (MDS). The source of material for this insertion could not be established, but did not arise from either a balanced deletion or translocation, and did not consist of constitutive heterochromatin as defined by C-banding. The same lesion was found in both sisters, both nephews and four of the five great-nephews. Of these, all were phenotypically and haematologically normal, with the exception of a great-nephew who at the age at the age of 6 exhibits features compatible with partial trisomy 16p. The relationship of the karyotypic abnormality to the MDS and partial trisomy 16p in this family is discussed.

Blood Cell Count↗
PubMed1988

Assessment of DNA content and cell cycle distribution of erythroid and myeloid cells from bone marrow.

A method is described for the measurement of DNA index and cell cycle distribution in purified erythroid and myeloid populations from human bone marrow. Erythroid cells were prepared after complement mediated lysis of non-erythroid marrow cells. Myeloid cells were obtained by fluorescence activated cell sorting by forward and wide angle light scatter. Mononuclear marrow cells were prepared with a density gradient. Nuclei prepared from the separated populations were stained with propidium iodide. Myeloid cells had a higher DNA index than erythroid cells, and the mononuclear preparation had an intermediate value. There were more erythroid than myeloid cells in the S and G2M phases of the cell cycle. These lineage differences are particularly relevant when considering data derived from unseparated bone marrow cells, and further experiments are needed to determine the origin of these anomalies.

Bone Marrow↗
PubMed1988

Implications for the practicing physician of the psychosocial dimensions of smoking.

The multifaceted nature of smoking includes its physiologic, social, and psychologic dimensions and its career features. It develops over time, through phases such as experimentation or conditioning. It also is given up over time, often after several unsuccessful attempts. Several repetitions of a sequence of considering cessation, attempting to quit, and relapsing are likely to precede permanent cessation. Those who are not ready to commit themselves to quitting may be reached by low-key information more than by too forceful exhortation. Those who are ready to quit may select from among a range of approaches, including group clinics, "self-help" manuals, and physician counseling. Maintenance requires as much attention as does cessation. Cooperation from those around the quitter, reminders to use skills for coping with stressors or temptations, and continued encouragement from the physician may all encourage long-term abstinence. Owing to the multifaceted nature of smoking and quitting and the multiple approaches to cessation and its maintenance, the physician may best be viewed as a catalyst for nonsmoking. If appropriate to his or her practice, this may include extended patient counseling, but those unable to provide this may still make great contributions through brief information on why it is important to quit, encouragement to do so, timely referral to other staff or to materials and programs available in the community, and continued expression of interest in the patient's efforts and/or success. All these may catalyze quitting without demanding excessive time or skills beyond those commonly employed by the physician. In catalyzing nonsmoking, the physician can also be an effective proponent of community or voluntary agency programs as well as institutional and governmental policies to limit smoking in health care facilities and public places. The American College of Chest Physicians' policy encouraging nonsmoking among its Fellows and in their offices is an excellent example of this catalyst role.

Adolescent↗
PubMed1988

A comparison of commercially available luminescence enhanced enzyme immunoassays with in-house non-radioisotopic assays for thyroxine binding globulin and total thyroxine.

Commercial luminescence enhanced enzyme immunoassays (Amersham-Amerlite) for thyroxine binding globulin (TBG) and total thyroxine (TT4) were compared with the in-house methods (TT4--Abbott TDx, TBG--Immunoluminometric Assay (ILMA)). The experimental groups consisted of 108 healthy euthyroid blood donors, 165 non-selected thyroid outpatients, 44 tumour bearers and 84 haemodialysis patients. Total thyroxine/thyroxine binding globulin quotients were constructed as an index of thyroid function. The luminescence enhanced enzyme immunoassays were precise (interassay coefficients of variation less than 10% in the range 5-45 mg/l thyroxine binding globulin and 20-100 micrograms/l for total thyroxine) performed similarly to the in-house methods in the differentiation of eu-, hypo- and hyperthyroidism on the basis of total thyroxine/thyroxine binding globulin quotients. Although statistically significant differences often occurred in comparisons of the in-house method with the luminescence enhanced enzyme immunoassays, these only gave rise to thyroid status differences in two cases out of 273, where the in-house method gave a hyperthyroid, the luminescence enhanced enzyme immunoassay a euthyroid answer, when taken from the total thyroxine/thyroxine binding globulin quotients. The luminescence enhanced enzyme immunoassays performed as well as the in-house methods, and quality assessment data were comparable with their radioimmunological counterparts.

Humans↗
PubMed1988

Enrichment of CD34 (My10)-positive myeloid and erythroid progenitors from human marrow and their growth in cultures supplemented with recombinant human granulocyte-macrophage colony-stimulating factor.

Myeloid and erythroid progenitor cells were enriched from human marrow by selecting CD34-positive (CD34 + ve) cells, labeled with the My10 (HPCA-1) antibody, using a fluorescence-activated cell sorter. Seventy-one percent of CD34 + ve cells were blasts and most of these were too primitive to be identified by standard morphological criteria. On average, 9.5% of CD34 + ve cells formed clones after 14 days of culture in semisolid medium supplemented with erythropoietin and medium conditioned by 5637 bladder carcinoma cells. Over 2.5% of CD34 + ve cells were day-14 myeloid colony-forming cells and 2.4% were erythroid colony (burst)-forming progenitors. The remaining progenitors formed myeloid and erythroid clusters. A subpopulation of day-14 myeloid colony-forming cells failed to respond to recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) after accessory cells were removed during enrichment, so it appears that this factor can induce myeloid growth indirectly as well as directly. Recombinant human GM-CSF also supported erythroid colony-formation in cultures of CD34 + ve cells, which suggests that this hemopoietin may act directly on erythroid progenitors.

Antigens, CD34↗
PubMed1988

RAS mutations in myelodysplasia detected by amplification, oligonucleotide hybridization, and transformation.

Members of the RAS gene family have been implicated in many neoplasms with activating mutations around amino acid positions 12 and 61. We have assessed the mutational activation of H, K, and NRAS in myelodysplasia (MDS) by polymerase chain reaction and hybridization with synthetic oligonucleotide probes. Using this method, point mutations in codons 12/13 and 61 of these RAS genes were detected in 20 of 50 patients including two with refractory anemia with ringed sideroblasts (RARS). Ten normal individuals had no detectable RAS mutations. In 11 instances, DNA from patients with detectable RAS mutations were shown to register in either NIH3T3 focus-forming or nude mouse tumorigenicity assays. In addition, one patient (RARS) was shown to have an activated NRAS gene detected by a tumorigenicity assay and Southern blot analyses. Two MDS patients had mutations detected in two different RAS genes. DNA from one of these patients was observed to give rise to transformants with activated N and HRAS. Two patients with detectable NRAS mutations in the MDS stage progressed to AML and DNA from the AML stage registered positively in a transformation assay with NRAS activation. These results show that RAS mutations can occur at early, as well as late, stages of leukemic progression. The incidence of RAS mutations appears to be significantly higher in CMML than in the other subgroups (p = 0.02).

Adult↗