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Biomedical subjects

J Bennett

Publications and source records attributed to J Bennett.

At least 19 recordsLinked to original sources
PubMed1992

c-myc and c-myb expression in acute myelogenous leukemia.

Monoclonal antibodies and flow cytometry were used to detect the expression of c-myc and c-myb in the bone marrow (BM) and peripheral blood (PB) cells of patients with acute myelogenous leukemia (AML). The expression of neither gene was correlated with the percent blast cells in the BM or PB nor was there a correlation between c-myc and c-myb expression. A wide range of expression of each gene was found within each FAB type of AML. Patients who had a high proportion of leukemia cells expressing c-myb were less likely to respond to remission induction therapy than patients in whom a low proportion of cells expressed c-myb. This association appears to reflect an inverse relationship between the proportion of cells expressing c-myb and the sensitivity of leukemia cells to the killing effects of chemotherapy in vivo. Treatment outcome was unrelated to c-myc expression.

Bone Marrow↗
PubMed1992

Translocation (2;9)(p12;p23) in a case of acute leukemia with t(4;11)(q21;q23). Lack of rearrangement of the kappa and interferon gene loci.

A case is reported of an adult male patient with acute leukemia characterized by the presence of the novel cytogenetic abnormality, t(2;9)(p12;p23), in addition to a t(4;11)(q21;q23). The immunophenotype of the blast cell population was consistent with immature early pre-B cell acute lymphoblastic leukemia (ALL) (TdT+,HLA-DR+,CD19+,CD24 +/-,CD10-) expressing myelo-monocytic antigens (CDw65,CD15). The genotype showed a clonal rearrangement of the immunoglobulin heavy chain locus. Because the immunoglobulin kappa (kappa) light chain gene is located on chromosome 2 at band p12 and interferon alpha (alpha) and beta (beta) map to chromosome 9p21-p22, rearrangements of these loci as a result of the t(2;9) were studied. There was no evidence for rearrangement of the region covering about 40 kilobases around the kappa locus when hybridized to C(kappa), the 3' kappa enhancer or the kappa deleting element. Only germline size restriction fragments were also found for the interferon alpha and beta genes. The patient's clinical features were typical for ALL associated with the t(4;11), including a high white blood cell count at presentation, hepatosplenomegaly, and a poor outcome. The potential significance of 2p and 9p abnormalities in addition to t(4;11) is discussed.

Adult↗
PubMed1992

A locus control region adjacent to the human red and green visual pigment genes.

Deletion of sequences 5' of the human red and green pigment gene array results in blue cone monochromacy, a disorder in which both red and green cone function are absent. To test whether these sequences are required for transcription of the adjacent visual pigment genes in cone photoreceptors, we produced transgenic mice carrying sequences upstream of the red and green pigment genes fused to a beta-galactosidase reporter. The patterns of transgene expression indicate that the human sequences direct expression to both long and short wave-sensitive cones in the mouse retina and that a region between 3.1 kb and 3.7 kb 5' of the red pigment gene transcription initiation site is essential for expression. Sequences within this region are highly conserved among humans, mice, and cattle, even though the latter two species have only a single visual pigment gene at this locus. These experiments suggest a model in which an interaction between the conserved 5' region and either the red or the green pigment gene promoter determines which of the two genes a given cone expresses.

Animals↗
PubMed1992

Oestradiol-induced hypotension in spontaneously hypertensive rats: putative role for intracellular cations, sodium-potassium flux and prostanoids.

1. The effect of oestradiol alone and in combination with indomethacin on blood pressure, erythrocyte cation concentration and Na(+)-K+ flux has been studied in adult female normotensive and spontaneously hypertensive rats. 2. Oestradiol alone resulted in a significant decrease in blood pressure in spontaneously hypertensive rats (from 165.3 +/- 3.9 to 146.4 +/- 2.7 mmHg, P less than 0.001), whereas it induced a significant increase in normotensive rats (from 111.8 +/- 1.8 to 124.1 +/- 3.6 mmHg, P less than 0.001). When indomethacin and oestradiol were administered simultaneously or when indomethacin was given alone, no change in blood pressure occurred in spontaneously hypertensive rats (158.6 +/- 6.9 and 159.8 +/- 6.2 mmHg, respectively). 3. The fall in blood pressure induced by oestradiol in spontaneously hypertensive rats was associated with significant reductions in erythrocyte K+ concentration (from 127.4 +/- 1.2 to 116.9 +/- 1.7 mmol/l of cells, P less than 0.001), in erythrocyte Na+ concentration (from 14.3 +/- 0.8 to 13.0 +/- 0.6 mmol/l of cells, P less than 0.02), in ouabain-sensitive erythrocyte Na+ flux (from 17.8 +/- 0.3 to 16.0 +/- 0.4 mmol h-1 (l of cells)-1, P less than 0.01) and in ouabain-sensitive erythrocyte K+ flux (from 11.4 +/- 0.2 to 10.4 +/- 0.2 mmol h-1 (l of cells)-1, P less than 0.01). No change in blood pressure, erythrocyte cation concentration or Na(+)-K+ flux occurred when oestradiol and indomethacin were given together or when indomethacin was administered alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Lymphoid lineage-associated features in acute myeloid leukaemia: phenotypic and genotypic correlations.

This study is intended to establish biological correlation between the expression of lymphoid associated features in acute myeloid leukaemia (AML). In 62 AML patients, predominantly enrolled on Eastern Cooperative Oncology Group (ECOG) treatment protocols, in whom immunoglobulin (Ig) as well as T-cell receptor beta chain (TCR-beta) gene rearrangement analyses had been performed, morphology, cytochemistry, antigen profile and karyotype were reviewed retrospectively. Nuclear reactivity with anti-TdT antibody was demonstrated in 34 patients (55%) and confirmed by ribonuclease protection assay in all patients tested. Five TdT-protein negative patients were TdT-transcript positive. Lymphoid antigens (lyA) were detected in 24 of 51 cases tested (47%) with B-cell antigens (CD19, CD10) being restricted to TdT+ AML (P = 0.03). Only two patients had Ig heavy, none had Ig light chain or TCR-beta gene rearrangements. Although both patients with rearranged Ig loci were TdT+, either by protein or RNA analysis, the low incidence of such rearrangement within the TdT+ AML group (6%) argues against a significant association between the presence of TdT and crosslineage Ig gene rearrangements in AML. While FAB-diagnoses did not differ between TdT+ and TdT- or lyA+ and lyA- AML, particular immunophenotypic features correlated with TdT positively, e.g. the presence of early antigens, CD34 and HLA-DR, and the absence of the more mature myelo-monocytic antigens, CDw65 and CD14. Certain cytogenetic abnormalities were associated with TdT+ AML such as inv(16) (p13q22) or t(16;16) (p12;q22) (five patients; P = 0.03) and t(8;21) (q22;q22) (three patients). A greater number of TdT- than TdT+ AML patients had only normal karyotypes (P = 0.06). Neither immunophenotypic nor karyotypic correlations could be established for lyA+ AML.

Acute Disease↗
PubMed1992

Relationship of [3H]Ara-C incorporation and response to therapy with high-dose Ara-C in AML patients: a Leukemia Intergroup study.

Pretherapy bone marrow (BM) aspirates of 143 patients with acute myeloid leukemia (AML) were incubated simultaneously with bromodeoxyuridine (BrdU) and tritiated cytosine arabinoside ([3H]Ara-C) to determine the labeling index (LI) and extent of [3H]Ara-C incorporation. Of 143 AML patients, 121 received high-dose Ara-C (HDAra-C) as a single agent for induction therapy (55 newly diagnosed, 66 in first relapse), whereas 22 received HDAra-C plus mAMSA. The data demonstrate that a subset of patients who will fail HDAra-C remission induction therapy because of drug-resistant disease can be prospectively identified on the basis of the low amount of Ara-C incorporated by their leukemia cells.

Acute Disease↗
PubMed1991

Tandem mass spectrometry identifies sites of three post-translational modifications of spinach light-harvesting chlorophyll protein II. Proteolytic cleavage, acetylation, and phosphorylation.

The photosynthetic membranes of spinach (Spinacia oleracea L.) chloroplasts were incubated with [gamma-32P] ATP. When the thylakoid membrane kinase was activated with light, the 25- and 27-kDa forms of the light-harvesting chlorophyll a/b protein (LHC II) were phosphorylated on their amino termini. Treatment of the membranes with proteinase K or thermolysin released phosphopeptides which were purified by ferric ion affinity chromatography and reverse phase high performance liquid chromatography. Sequencing of the phosphopeptides was performed with tandem quadrupole mass spectrometry. Three different phosphopeptides Ac-RKTAGKPKT, Ac-RKTAGKPKN, and Ac-RKSAGKPKN originating from class I LHC II were examined after release by thermolysin. One phosphopeptide, Ac-RRTVKSAPQ, originating from class II LHC II was examined after release by proteinase K. Each of the four LHC II phosphopeptides was derived from the amino terminus of a distinct protein. Peptides were acetylated at their amino-terminal arginine and were phosphorylated on either threonine or serine in the third position. We conclude that proteolytic processing of pre-LHC II occurs at a conserved methionyl-arginyl bond and is followed by amino-terminal acetylation of the arginine and nearby phosphorylation of the mature LHC II. Eight different peptides were synthesized in acetylated and nonacetylated forms as substrates for the thylakoid membrane kinase. From a comparison of the kinetics of phosphate incorporation into the peptides, we conclude that basic residues on both sides of the phosphorylation site are important for enzyme recognition. Acetylation of the amino terminus is not required for phosphorylation.

Acetylation↗
PubMed1991

Synthetic analogues of a transit peptide inhibit binding or translocation of chloroplastic precursor proteins.

Although amino-terminal transit peptides of chloroplastic precursor proteins are known to be necessary and sufficient for import into chloroplasts, the mechanism by which they mediate this process is not understood. Another important question is whether different precursors share a common transport apparatus. We used 20-residue synthetic peptides corresponding to regions of the transit peptide of the precursor to the small subunit of ribulose bisphosphate carboxylase (prSS) as competitive inhibitors for the binding and translocation of precursor proteins into chloroplasts. Synthetic peptides with sequences corresponding to either end of the transit peptide had little to no effect on binding of prSS to chloroplasts, but significantly inhibited its translocation. Synthetic peptides corresponding to the central region of the transit peptide inhibited binding of prSS to chloroplasts. Each of the peptides inhibited binding or translocation of precursors to light-harvesting chlorophyll a/b protein, ferredoxin, and plastocyanin in the same manner and to a similar extent as prSS transport was inhibited. The results presented in this paper suggest that the central regions of the transit peptide of prSS mediate binding to the chloroplastic surface, whereas the ends of this transit peptide are more important for translocation across the envelope. Furthermore, all of the precursors tested appear to share components in the transport apparatus even though they are sorted to different chloroplastic compartments.

Amino Acid Sequence↗
PubMed1991

Cell cycle and clinical characteristics of patients with acute myeloid leukemia and myelodysplasia whose biopsies are reactive with anti-factor VIII antibody. A Leukemia Intergroup Study.

Presence of megakaryocytic cells in patients with myeloid disorders were investigated by staining plastic embedded biopsy sections with an anti-Factor VIII antibody (AFA). Two hundred and fifty cases were studied, 207 of whom had acute myeloid leukemia (AML) while 43 had myelodysplastic syndromes (MDS). Abnormal clusters of AFA positive cells indicating multilineage disease were identified in 17% with primary AML (30/175), 38% with secondary AML (12/32) and 42% cases of MDS (18/43). Biological characteristics of these 60 AFA positive cases were investigated. No unique differences in cell cycle characteristics following bromodeoxyuridine (BrdU) were identified. We confirm several recent reports that the incidence of multilineage involvement in AML is substantial.

Adult↗
PubMed1991

Unusual topography of bovine rhodopsin promoter-lacZ fusion gene expression in transgenic mouse retinas.

To define the cis-acting DNA elements required for rhodopsin expression, we generated lines of transgenic mice carrying sequences upstream of the bovine rhodopsin gene fused to the E. coli beta-galactosidase gene (lacZ). Upstream sequences extending from -2174 to +70 bp, from -734 to +70 bp, and from -222 to +70 bp direct photoreceptor-specific expression. All three -2174 lines demonstrate a superior-temporal to inferior-nasal gradient of expression across the retina, whereas lines carrying the shorter constructs demonstrate either spatially continuous expression across the retina, discrete clusters of expression, or both. As a complementary approach to defining regulatory elements, we compared DNA sequences 5' of the murine, bovine, and human rhodopsin genes. Significant homology between all three species was found just upstream of the transcription start site and at approximately 1.5 kb upstream.

Aging↗