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J Rees

Publications and source records attributed to J Rees.

At least 91 records · Page 5Linked to original sources
PubMed1991

A retinoic acid response element is present in the mouse cellular retinol binding protein I (mCRBPI) promoter.

Genomic and cDNA sequences for the mouse cellular retinol binding protein I (mCRBPI) are presented. A specific cis-acting element responsible for retinoic acid (RA) inducibility of the mCRBPI promoter was identified and characterized. Deletion mapping of a CRBPI promoter--chloramphenicol acetyltransferase reporter gene construct localized this element to a 259 bp restriction fragment located approximately 1 kb upstream from the transcription start-site. A sequence closely resembling the previously characterized RA response element (RARE) of the RA receptor beta 2 (RAR-beta 2) promoter, and consisting of a direct repeat of the motif 5'-GGTCA-3' separated by three nucleotides, was found within this restriction fragment. Mutation of these 5'-GGTCA-3' motifs to GGAGC and GGGGC abolished RA-inducible transcription whereas a mutation to a direct repeat of the GTTCA motif found in the RARE of the RAR-beta 2 promoter resulted in enhanced inducibility. Oligonucleotides containing the direct repeat of the GGTCA motif were able to confer RA-dependent transcriptional enhancement to the herpes simplex thymidine kinase promoter, as well as to bind directly all three retinoic acid receptors (RARs) alpha, beta and gamma, as determined by gel retardation/shift assays. The control of CRBPI gene transcription by RA-RAR complexes interacting with the RARE characterized here may correspond to a feedback mechanism important in regulating retinoid metabolism and action.

Amino Acid Sequence↗
PubMed1991

In-situ hybridization using digoxigenin-labelled probes in human skin.

This study demonstrated that in-situ hybridization using digoxigenin-labelled oligonucleotide poly-T probes and digoxigenin-labelled riboprobes for keratin 14 is possible on routinely fixed paraffin-embedded sections. The resolution and time course of the detection system compared favourably with isotopically labelled probes. Major differences were shown in keratinocyte messenger RNA content with differentiating cells expressing high levels when compared with the basal layers. Previous work on the distribution of keratin 14 messenger RNA was confirmed and we were able to show that using non-isotopic in-situ hybridization, sensitive and accurate cellular localization was feasible in skin sections.

Digoxigenin↗
PubMed1990

The separation and detection of alkaline oligoclonal IgG bands in cerebrospinal fluid using immobilised pH gradients.

A method is described for the separation and detection of highly alkaline IgG bands in unconcentrated cerebrospinal fluid (CSF). These bands are frequently found in the cerebrospinal fluid of patients with inflammatory diseases of the central nervous system, particularly in the case of multiple sclerosis, and their detection is an important aid in clinical diagnosis. An isoelectric focusing technique using an immobilised pH gradient in polyacrylamide gel has been developed over the pH range 7-10, producing a linear and stable pH gradient with excellent resolution. After electrofocusing, the protein patterns were blotted onto polyvinylidene difluoride membranes and visualised using anti-human IgG followed by an enzyme-labelled second antibody. Blotting could be carried out by capillary diffusion for up to 16 h duration without any loss in resolution. Using this method, highly alkaline intrathecal IgG bands were found in the cerebrospinal fluid of all of the 14 multiple sclerosis patients. There were also 2 patients with alkaline IgG bands in their cerebrospinal fluid who were not diagnosed as multiple sclerosis. By contrast, no alkaline IgG bands with an isoelectric point (pI) greater than 8.6 were found in any of the serum samples studied (n = 50) from patients with various neurological disorders including multiple sclerosis.

Buffers↗
PubMed1990

Triple combination of retinoic acid plus actinomycin D plus dimethylformamide induces differentiation of human acute myeloid leukaemic blasts in primary culture.

Differentiation induction therapy provides an alternative for treatment of acute myeloid leukaemia (AML) patients who are either unsuitable for or unresponsive to conventional cytotoxic chemotherapy. The effect of a triple combination of retinoic acid (RA) + actinomycin D (Act-D) + dimethylformamide (DMF) on differentiation of blasts from 24 AML patients was studied. Non-adherent mononuclear cells were seeded at a concentration of 5 x 10(5) cells/ml in 24-well tissue-culture plates containing RPMI 1640 culture medium with 20% fetal calf serum, 10% autologous serum and 10% 5637-conditioned medium and incubated with 10(-6) M retinoic acid, 5 nM actinomycin D and/or 100 mM dimethylformamide alone and in combination with each other for 6 days at 37 degrees C in a humidified incubator and an atmosphere containing 5% CO2. The triple combination of 10(-6) M retinoic acid + 5 nM actinomycin D + 100 mM dimethylformamide induced 90% of the blasts from 22 of the 24 AML patients to differentiate. The combination of N-methylformamide (a compound similar to dimethylformamide) with cyclophosphamide significantly increased the in vivo activity with no concomitant increase in its reversible hepatotoxicity. Since several polar compounds related to dimethyl-formamide, e.g. hexamethylene bisacetamide and N-methylformamide, are currently undergoing phase II clinical trials, it may be feasible to combine one of these with retinoic acid and/or actinomycin D in the treatment of AML patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Triple combination of retinoic acid + 6-thioguanine + hexamethylene bisacetamide induces differentiation of human AML blasts in primary culture.

Differentiation induction therapy provides an alternative therapeutic approach for patients with acute myeloid leukaemia (AML) who are either unsuitable for or unresponsive to conventional cytotoxic chemotherapy. The effect of a triple combination of retinoic acid (RA) + 6-thioguanine (6-Th) + hexamethylene bisacetamide (HMBA) on differentiation of blasts from 24 AML patients was studied. Nonadherent mononuclear cells were seeded at a concentration of 5 x 10(5) cells/ml in 24-well tissue culture plates containing RPMI-1640 culture medium with 20% fetal calf serum and 10% 5637-conditioned medium and incubated with 10(-6) M retinoic acid, 1.5 X 10(-6) M 6-thioguanine and/or 2 mM hexamethylene bisacetamide for six days at 37 degrees C in a humidified incubator under 5% CO2. Morphological, cytochemical and functional differentiation into mature cells were induced in blasts from 22 out of the 24 AML patients following exposure to the triple combination of 10(-6) M RA + 1.5 X 10(-6) M 6-Th + 2 mM HMBA in primary culture. These effective results justify a clinical trial of such triple combination for AML patients who are either unsuitable for or unresponsive to conventional cytotoxic chemotherapy.

Acetamides↗
PubMed1990

Influenza A and rhabdomyolysis.

A case of influenza A H3N2 resulting in unusually severe rhabdomyolysis and myoglobinuria is described. Although a rare complication of viral infection, prompt treatment with intravenous fluids can prevent the serious complications which may follow.

Adult↗
PubMed1990

Radiography of the paranasal sinuses--one or three views?

A prospective study of 100 adult patients undergoing paranasal sinus radiography was performed. Two experienced radiologists independently assessed a single occipitomental view and, at a later date, the traditional three projections, i.e. occipitomental, occipitofrontal and lateral. There was 99% intra-observer agreement between the diagnosis on a single projection compared with all three films. In five cases, the frontal sinuses were difficult to assess mainly due to poor radiography, and in defined circumstances additional views may be required occasionally. We conclude that with greater attention to radiographic technique the occipitomental view alone is sufficient for diagnostic purposes.

Adolescent↗
PubMed1990

Low-dose exposure to antigen induces sub-clinical sensitization.

We examined the effects of a small initial sensitizing dose of antigen (dinitrochlorobenzene, DNCB) on the subsequent response to a second, defined sensitizing stimulus. The second stimulus was actually the regimen of four doses of DNCB (3.125, 6.25, 12.5, and 25 micrograms) normally used as the elicitation challenge. In two separate experiments 13 and 18 control subjects received an initial 'challenge' with the four doses to induce sensitivity, and 4 weeks later their responses were determined with a second, elicitation challenge. Two groups of 12 and 15 experimental subjects received an initial dose predicted to induce clinically detectable sensitivity in 50% or 25%, respectively. Four weeks later, their responsiveness was determined with quantitative challenge and the subjects who gave no response received a further challenge 4 weeks later. Their responses, compared with those from the control subjects, were augmented, indicating that sub-clinical priming of the immune system had indeed occurred.

Analysis of Variance↗
PubMed1990

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Conservation of Natural Resources↗
PubMed1990

Contact sensitivity to dinitrochlorobenzene is impaired in atopic subjects. Controversy revisited.

If there is a primary dysfunction of the immune system in atopic eczema it might be reflected in altered capacity to generate delayed-type hypersensitivity. Therefore, the dose-response relationships for contact sensitization were determined for 22 patients (10 men) with minimal atopic eczema and compared with those from 27 nonatopic, healthy control subjects (12 men). Sensitization was induced with 30 micrograms of dinitrochlorobenzene applied to the thigh. Four weeks later the subjects were challenged with three doses of dinitrochlorobenzene (8.8, 12.5, and 17.7 micrograms), and responses were quantified with calipers as change in skinfold thickness at 48 hours. Atopic patients were significantly less responsive with smaller reactions at all challenge doses and a flatter challenge dose-response curve than that for control subjects. Thus, proper quantitative comparisons have shown that subjects with minimal atopic eczema do not mount a normal contact hypersensitivity response. However, it is not clear whether this is a consequence of the atopic state per se or is related to the presence of even a minor degree of eczema.

Adolescent↗
PubMed1989

Differentiation induction therapy of myelodysplastic syndromes.

Myelodysplastic syndromes are a heterogenous group of haemopoietic stem cell disorders characterized by dysplastic haematopoiesis and a defective maturation of a slowly expanding or sometimes of a stable population of haemopoietic progenitors. Defective maturation, which may involve one or more of the marrow cell lineages is regarded as the central pathophysiological feature of myelodysplastic syndromes. Patients with myelodysplastic syndromes respond poorly to conventional cytotoxic chemotherapy, frequently developing a prolonged marrow aplasia. The alternative and more appropriate form of therapy is differentiation induction therapy. The results of few preliminary clinical studies in myelodysplastic patients showed that a combination of differentiating agents is superior to single agent differentiation therapy. An extensive pre-clinical screening of the response of fresh cells from myelodysplastic patients in primary culture is needed to establish the optimal doses and conditions for significant synergies between various differentiating agents followed by large controlled randomized clinical trials based on differentiation induction therapy for patients with myelodysplastic syndromes.

Cell Differentiation↗
PubMed1989

Cooperative effects of human recombinant granulocyte-macrophage colony stimulating factor and human recombinant erythropoietin in inducing erythroid differentiation of the human erythroleukaemia cell line K 562 clonogenic cells.

Human acute erythroleukaemia arises from the inability of the haemopoietic stem cell to differentiate. K 562 cell line provides a homogeneous population of primitive erythroleukaemic cells that are at the same point of differentiation. The effect of human recombinant granulocyte-macrophage colony-stimulating factor and human recombinant erythropoietin on the differentiation of K 562 clonogenic cells was studied. Cells were cultured in methylcellulose culture for 5 days at 37 degrees C in humidified atmosphere containing 5% CO2 in air and scored for erythroid differentiation by benzidine staining. A combination of both growth factors induced erythroid differentiation in more than 80% of K 562 clonogenic cells. This combination may be useful in the treatment of patients with erythroleukaemia.

Cell Differentiation↗