Search PubMed⌕ Search

Biomedical subjects

A Jacobs

Publications and source records attributed to A Jacobs.

At least 145 records · Page 8Linked to original sources
PubMed1991

Transcriptional interference in transgenic plants.

When a promoterless marker gene is transformed into the plant genome using the Agrobacterium vector system, on average 30% of the T-DNA inserts produce gene fusions. This suggests that the T-DNA is preferentially integrated into transcribed regions. Here, we proposed that this transcriptional activity is responsible for some of the variation in expression frequently observed among independent transformants. Using hybrid gene constructions, we show that transcriptional readthrough into a downstream gene with opposite orientation substantially reduces expression of this gene both in transient expression and in transgenic plants. Furthermore, a poly(A) signal/terminator can block readthrough and restore the expression of the gene. Finally, enzymatic analysis of calli suggests that less variation in neomycin phosphotransferase II synthesis is observed when the gene is separated from plant DNA by promoter and terminator elements.

Agrobacterium tumefaciens↗
PubMed1991

Heterotropic interactions in aspartate transcarbamoylase: turning allosteric ATP activation into inhibition as a consequence of a single tyrosine to phenylalanine mutation.

Aspartate transcarbamoylase (EC 2.1.3.2) is extensively studied as a model for cooperativity and allostery. This enzyme shows cooperativity between the catalytic sites, and its activity is feedback inhibited by CTP and activated by ATP. These regulatory processes involve several interfaces between catalytic and regulatory chains as well as between domains within these two types of chains. As far as the regulatory chain is concerned, its two domains are in contact through a hydrophobic interface, in which a tyrosine residue is inserted in a pocket involving two leucine residues of the allosteric domain and a valine and a leucine residue of the zinc domain. To probe the possible implication of this hydrophobic core in the CTP and ATP regulatory effect, the tyrosine was replaced by a phenylalanine through oligonucleotide-directed mutagenesis. Interestingly, the resulting mutant shows a complete inversion of the ATP effect; it is now inhibited by ATP instead of being activated by this nucleotide triphosphate. This mutant remains normally sensitive to the feedback inhibitor CTP. This result shows that the hydrophobic interface between the two domains of the regulatory chain plays an important role in the discrimination between the regulatory signals promoted by the two allosteric effectors.

Adenosine Triphosphate↗
PubMed1991

Increased circulating colony-stimulating factor-1 in patients with preleukemia, leukemia, and lymphoid malignancies.

Recently, several malignant cell types have been reported to express colony-stimulating factor-1 (CSF-1) transcripts; however, the clinical significance of CSF-1 in malignancy has not been investigated. Using a CSF-1 radioimmunoassay, we surveyed concentrations of biologically active CSF-1 in the peripheral blood of 316 patients with malignant and premalignant hematologic disorders; 75 had a myelodysplastic syndrome (MDS), 12 acute myelogenous leukemia (AML), 7 chronic myelogenous leukemia, 21 chronic lymphocytic leukemia (CLL), 106 non-Hodgkin's lymphoma (NHL; of low-, intermediate- and high-grade malignancy), 46 Hodgkin's disease (HD), 46 multiple myeloma (MM), and 3 monoclonal gammopathy of undetermined significance. Controls were 64 healthy subjects. The CSF-1 concentration was correlated with the type of disease, status of the disease, treatment status, and hematologic parameters. CSF-1 concentration was significantly elevated in 83.5% of the patients with active disease, and for each active disease group it was significantly greater (P less than .0001) than in the control. Thus, the high circulating CSF-1 concentration was not associated with a particular malignant phenotype or MDS subtype, but did correlate with the disease activity of both NHL and HD, and the tumor burden in MM, AML, and CLL. There was no correlation of the CSF-1 level with total counts of monocytes or neutrophils in patients with MDS or other malignancies. The cellular basis for the elevated circulating CSF-1 was not investigated. However, the results are consistent with the possibility that the premalignant or malignant cells themselves produce CSF-1 or regulate its production by normal cells.

Biomarkers, Tumor↗
PubMed1991

Determination of beta 2-receptor agonists in bovine urine and liver by gas chromatography-tandem mass spectrometry.

A highly specific and sensitive method for the simultaneous detection of seven beta 2-receptor agonists in bovine liver homogenates and urine was developed. A 10-g amount of liver was homogenized and treated with Subtilisin A. The resulting enzymatic digest was extracted with tert.-butanol-ethyl acetate (3:7) and the crude extract was purified on a 6-ml Bakerbond alumina neutral disposable extraction column. Subsequently, the hydrous eluate from the alumina column was buffered at pH 6 and loaded on top of a preconditioned 3-ml Bond-Elut Certify column. Urine was buffered and loaded onto a 3-ml Certify column without pretreatment. The analytes were eluted with dichloromethane-isopropanol (8:2) containing 2% ammonia. The extract obtained was trimethylsilylated and analysed by gas chromatography-tandem mass spectrometry using multiple selected reaction monitoring. The limits of detection for the beta 2-receptor agonists evaluated were between 0.5 and 5 ppb.

Adrenergic beta-Agonists↗
PubMed1991

The acceptability of behavioral and emotional feedback depending upon valence and structure in personal growth groups.

Forty-eight students participated in a one-time personal growth group. Subjects were assigned to one of eight groups. Exercises were conducted to promote interpersonal contact, followed by feedback sessions. Four groups generated and exchanged feedback among group members. Statement lists were used as feedback in remaining groups. Within each set, one group delivered positive-behavioral; one, positive-emotional; one, negative-behavioral; and one, negative-emotional feedback. Positive feedback was more credible, desirable, and influential for recipients and donors; positive-behavioral feedback in particular was more credible. Donors rated unstructured feedback as more credible than structured feedback, with negative-structured feedback the least credible with donors and recipients. Findings are discussed in terms of research and application.

Adult↗
PubMed1991

Colony-cluster ratio and cluster number in cultures of circulating myeloid progenitors as indicators of high-risk myelodysplasia.

Circulating myeloid progenitors were assayed in 172 normal subjects and 147 patients with myelodysplastic syndrome (MDS). Patients whose cultures had colony/cluster ratios (CCR) less than 0.3 had significantly shorter survival periods than comparable patients with CCR greater than 0.3. A second prognostic indicator, which complemented CCR, was identified in patients with less than 5% blasts. Median survival was significantly reduced in patients with greater than 15 clusters/ml blood despite colony and cluster numbers being predominantly within the normal range. Characteristic differences were found in three FAB groups large enough to allow statistical analysis. Survival amongst patients with refractory anaemia with excess of blasts (RAEB) was related to CCR and was independent of cluster number. Amongst sideroblastic patients (SA) survival related only to cluster number. Refractory anaemia (RA) patients included individuals in both high-risk groups with only three patients out of 64 showing both features. Amongst all the MDS patients, those with CCR greater than 0.3 and less than 15 clusters/ml blood formed a low-risk group (n = 60) with a relatively good prognosis of whom 85% survived the study period (median duration 938 d) including 94% of those in this group with less than 5% marrow blast cells.

Cell Aggregation↗
PubMed1991

The treatment of anaemia in the myelodysplastic syndromes with recombinant human erythropoietin.

Recombinant human erythropoietin was administered subcutaneously to 10 patients with myelodysplasia (MDS) who had haemoglobin concentrations less than 10 g/dl, in an attempt to relieve their anaemia. Doses of 60 units/kg/d rising to 90 units/kg/d were given over a maximum period of 16 weeks. Two out of 10 patients showed a steady rise in haemoglobin concentration during treatment. One patient with refractory anaemia had a sustained rise from 9.9 g/dl to 11.3 g/dl, and one patient with refractory anaemia with excess blasts (RAEB) had a rise from 9.5 g/dl to 11.4 g/dl but then relapsed with the development of an iron deficient state. Serum concentrations of immunoreactive EPO varied considerably between patients, but both responders had relatively low baseline levels. Both responders were also new diagnoses and had received no red cell transfusions. The criteria for response to recombinant human erythropoietin therapy, as well as the indications for therapy remain to be clarified.

Adult↗
PubMed1991

Growth response to cytokines of circulating myeloid progenitors from myelodysplastic patients at diagnosis and more than 600 days after diagnosis.

Myeloid colony growth from the peripheral blood of myelodysplastic (MDS) patients was assessed for abnormal in vitro response to haemopoietic growth factors (granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 (IL-1), interleukin-3 (IL-3)). Abnormal colony growth, increased or reduced, was observed with each of the factors. No specific growth pattern was related to any of the French-American-British classification (FAB) types of disease. MDS patients who had survived greater than 600 days after diagnosis (n = 34) showed significantly fewer abnormalities than patients assayed at the time of diagnosis (n = 37), the major difference being less frequent stimulation of colony growth. These findings indicate that the time of sampling relative to diagnosis needs to be considered when interpreting the in vitro response to growth factors of myeloid colonies from MDS patients.

Bone Marrow↗
PubMed1991

Increased drug accumulation ex vivo with cyclosporin in chronic lymphatic leukemia and its relationship to epitope masking of P-glycoprotein.

The ability of cyclosporin to modify drug accumulation in vitro, measured by the cellular accumulation of daunorubicin, was examined. In 42 patients with chronic lymphatic leukaemia this correlates well with the levels of P-glycoprotein (Pgp) measured by immunofluorescent labelling of Pgp after treatment of the cells with neuraminidase to unmask the epitope recognized by the monoclonal antibody MRK 16. It is shown that flow cytometric analysis using MRK 16 to detect Pgp expression levels together with drug accumulation studies can rapidly assess the multidrug-resistant phenotype of patients' cells, and enable selection of those suitable for therapy with agents known to circumvent mdr-1 mediated drug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

The clearance of a single i.v. bolus of recombinant human erythropoietin from the serum of patients with myelodysplastic syndromes and its effects on erythropoiesis.

The serum erythropoietin (EPO) concentration in patients with myelodysplasia (MDS) varies widely at similar hemoglobin concentrations, although the reasons for this variation are unclear. We have studied the pharmacokinetics of an i.v. bolus of recombinant human EPO in ten subjects with myelodysplasia. Basal serum EPO concentration varied from 210 to 5984 mU/ml. Plasma half-time clearance (t1/2) varied from 3.9 to 20.0 h. A significant positive correlation was found between t1/2 and basal EPO concentration. An increase in immature peripheral blood reticulocytes was found on days 1 and 2 after EPO treatment; this may represent either an effect on hemopoiesis or on reticulocyte release from the bone marrow.

Aged↗