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Biomedical subjects

A Mather

Publications and source records attributed to A Mather.

At least 19 recordsLinked to original sources
PubMed2000

A RIA combined with SPE for the determination of a dual D2-receptor and beta2-adrenoceptor agonist, AR-C68397XX, in human plasma.

A radioimmunoassay has been developed for the determination of AR-C68397XX, a dual D2-receptor and beta2-adrenoceptor agonist, in human plasma. The method incorporates solid phase sample extraction and is suitable for the determination of the analyte at pg ml(-1) concentrations. The antiserum was raised in Suffolk cross sheep following primary and booster immunisations with an immunogen prepared by conjugating a carboxyphenylmethyl derivative of AR-C68397XX, to bovine serum albumin. The radioligand was prepared by the 125I-labelled iodination of a derivative of AR-C68397XX. The solid phase extraction procedure, using octadecyl sorbent, was introduced to remove matrix interferences in the plasma and to enhance method sensitivity. The calibration range is 20-500 pg ml(-1), using 0.5 ml of undiluted human plasma sample.

Adrenergic beta-2 Receptor Agonists↗
PubMed1999

Binding of [3H]desglycinyl remacemide to rat brain membranes: association with the benzomorphan attachment site of the N-methyl-D-aspartic acid receptor channel.

Desglycinyl remacemide (DGR), a biologically active metabolite of remacemide, was radiolabeled in an attempt to develop a ligand binding assay to identify its site of action. Incubation of the radioligand with membranes obtained from P2 fractions of whole rat brain revealed a single population of specific [3H]-DGR binding sites having a Kd of 290 nM and a Bmax of 1.3 pmole/mg protein. The specific binding of [3H]-DGR is most enriched in the P2 subcellular fraction and is heterogeneously distributed throughout the brain. The binding of [3H]-DGR to rat brain membranes was inhibited most potently by MK-801 and SKF-10,047. In contrast, haloperidol, and other sigma receptor-active agents, were relatively inactive at this site. These data suggest that DGR interacts with a channel blocking site on the NMDA receptor.

Animals↗
PubMed1995

Uniparental isodisomy for chromosome 16 in a growth-retarded infant with congenital heart disease.

We report a growth-retarded infant with congenital heart disease and maternal isodisomy for chromosome 16. Non-mosaic trisomy 16 was detected at mid-trimester chorionic villus sampling, performed because biochemical screening indicated an increased Down's syndrome risk. Further karyotyping analysis of the placenta, after delivery, showed a 50 per cent mosaic trisomy 16. The infant had an atrioventricular (A-V) canal defect, scoliosis, and several minor dysmorphic features. Although uniparental disomy for chromosome 16 has been reported previously, to our knowledge this is the first case of uniparental isodisomy for chromosome 16 which has been investigated with multiple DNA probes.

Abnormalities, Multiple↗
PubMed1992

Targeting of tumor cells and DNA by a chlorambucil-spermidine conjugate.

Many tumor cells, including murine ADJ/PC6 plasmacytoma cells, possess an active energy dependent polyamine uptake system which selectively accumulates endogenous polyamines and structurally related compounds. We have attempted to target the cytotoxic drug chlorambucil to a tumor possessing this uptake system by conjugating it to the polyamine spermidine. Furthermore, since polyamines have a high affinity for DNA, the attachment of spermidine to chlorambucil should also facilitate its targeting to DNA. This was supported by the observation that the chlorambucil-spermidine conjugate was approximately 10,000-fold more active than chlorambucil at forming interstrand crosslinks with naked DNA. In vitro cytotoxicity and in vivo antitumor studies were carried out using the ADJ/PC6 plasmacytoma. In vitro, using [3H]thymidine incorporation to assess cell viability following a 1-h exposure to control and polyamine depleted ADJ/PC6 cells, chlorambucil-spermidine was 35- and 225-fold, respectively, more toxic than chlorambucil. The increased toxicity of the conjugate compared to chlorambucil was possibly due to enhanced DNA binding and/or facilitated uptake via the polyamine uptake system. The enhanced toxicity of the conjugate but not chlorambucil by prior polyamine depletion with difluoromethylornithine, together with the observation that the conjugate but not chlorambucil competitively inhibited spermidine uptake into tumor cells, supported the suggestion that the conjugate utilized the polyamine uptake system. In vivo following a single i.p. dose, the conjugate was 4-fold more potent than chlorambucil in its ability to inhibit ADJ/PC6 tumor growth in BALB/c mice. However, the therapeutic index was not increased. Our results support the hypothesis that polyamines linked to cytotoxics facilitate their entry into tumor cells possessing a polyamine uptake system and increase their selectivity to DNA. This may have therapeutic application in the delivery of cytotoxic agents linked to polyamines to certain tumors.

Animals↗
PubMed1992

Uptake and cytotoxicity of novel nitroimidazole-polyamine conjugates in Ehrlich ascites tumour cells.

A number of tumour cells, including Ehrlich ascites tumour cells (EATC), possess a polyamine uptake system which selectively accumulates endogenous polyamines and structurally related compounds by an active energy dependent system(s). We suggest that it may be possible to utilize this uptake system to target certain cytotoxic agents to those tumour cells possessing this system. In an initial attempt to determine the feasibility of this suggestion, we have synthesized a series of 2- and 5-nitroimidazoles linked to polyamines and determined their ability to utilize the polyamine uptake system. Within the limited series of compounds synthesized, 2-nitroimidazole-polyamine conjugates were more potent inhibitors of spermidine uptake into EATC than the 5-nitroimidazole conjugates. It has been assumed partly based on the competitive nature of this inhibition, that the ability of these compounds to inhibit spermidine uptake is also a measure of their ability to be accumulated by EATC. A greater than 700-fold variation was observed in the ability of different analogues to inhibit spermidine uptake. The most potent inhibitors retained certain structural characteristics similar to those of spermidine. Those compounds linked to polyamines were much more potent inhibitors of polyamine uptake than the parent nitroimidazoles i.e. metronidazole and misonidazole. The toxicity of the parent compounds and their polyamine conjugates in control and polyamine-depleted EATC was assessed by measuring inhibition of tritiated thymidine incorporation. Polyamine depletion, by prior exposure to difluoromethylornithine, results in a compensatory increase in the uptake of polyamines and related structures which may result in an increase in toxicity. Whilst many of the novel conjugates showed only little or moderate toxicity to control cells, the toxicity of several of the conjugates but not the parent nitroimidazoles increased in the polyamine-depleted cells. A clear distinction was also observed between the ability to inhibit spermidine uptake (and hence affinity for the uptake system) and toxicity, e.g. compound 430, a dinitroimidazole-polyamine conjugate, was the best inhibitor of spermidine uptake studied but showed no toxicity. These results support the hypothesis that linking polyamines to nitroimidazoles facilitates the entry of the latter into cells, such as EATC, which possess the polyamine uptake system and may therefore have therapeutic application in the delivery of polyamine-linked cytotoxics to certain tumours.

Animals↗
PubMed1992

A hereditary immunodeficiency characterized by CD8+ T lymphocyte deficiency and impaired lymphocyte activation.

An unusual form of severe combined immunodeficiency in children from two different families was associated with absence of CD8+ T lymphocytes and normal numbers of CD4+ T lymphocytes that did not respond to stimulation by non-specific mitogens, specific antibodies against T cell receptor or specific antigens. The defect in the CD4+ cells was bypassed by activating agents which are independent of the T cell receptor. The combination of an activation defect and selective depletion of CD8+ T lymphocytes suggests that the defective pathway is important in the differentiation of immature thymocytes as well as the proliferation of mature lymphocytes.

Blood Cells↗
PubMed1987

Effect of cyclosporin, previous third-party transfusion, and pregnancy on antibody development after donor-specific transfusion before renal transplantation.

Non-cytotoxic and cytotoxic antibodies were sought after donor-specific transfusion (DST) in 12 potential renal transplant recipients given concomitant cyclosporin therapy and 13 given DST alone. Non-cytotoxic antibodies, which have been shown to develop after third-party transfusion and to be associated with successful transplantation, developed after DST whether or not cyclosporin was given. Donor and panel reactive lymphocytotoxic antibodies developed relatively infrequently after DST with or without cyclosporin. Donor-specific sensitisation occurred only in patients who were multiparous or had over 10 third-party transfusions. Non-cytotoxic Fc-receptor-blocking antibodies may play a part in the improved survival of one-haplotype-mismatched transplants pretreated with DST.

Antibodies↗
PubMed1986

Interlaboratory testing of the transferability of a candidate reference method for total cholesterol in serum.

In 1975 the Centers for Disease Control, in cooperation with the American Association for Clinical Chemistry Cholesterol Reference Method Study Group, began an investigation to develop a reference method for total cholesterol. Five potential reference methods were compared with the definitive method developed by the National Bureau of Standards before the chemical method of Abell et al. (J Biol Chem 1952;195:357-66) was selected as the recommended reference method. Because acceptance of a proposed reference method depends so greatly on the method's capability for transfer to other laboratories by written specifications and instructions, a transferability testing study was designed and conducted with 14 laboratories. The study consisted of preliminary testing of readiness of equipment, reagents, and personnel followed by transferability testing with eight runs on 10 serum pools. Laboratoires that did not meet readiness specifications had higher CVs in the transferability testing. The study demonstrated that the proposed method permits laboratories to attain a CV of less than 1.5% for one laboratory and of less than 3.0% among laboratories. The mean percent bias value was less than 1.0% for six of the 14 laboratories, less than 1.5% for 12, and less than 3.0% for all 14 laboratories.

Calibration↗
PubMed1984

International Federation of Clinical Chemistry (IFCC). Scientific Committee, Analytical Section. IFCC/WHO principles and recommendations on evaluation of diagnostic reagent sets used in health laboratories with limited resources. Part 3. Selection and evaluation using reference materials. General considerations.

The purpose of this document is to provide general considerations for the selection and evaluation of clinical chemistry kits in laboratories with limited resources. Separate documents have been developed to provide guidance on experimental procedure, the statistical treatment and interpretation of the data and criteria for acceptable performance of diagnostic kits designed to measure specific analytes.

Drug Labeling↗
PubMed1981

A candidate reference method for determination of total protein in serum. II. Test for transferability.

The transferability of the candidate Reference Method for total serum protein was tested in eight laboratories in the United States and Europe. National Bureau of Standards SRM 927 (bovine serum albumin) was used in each analytical run as the calibration standard. The mean absorptivity value obtained for this material was 0.2983 L g-1 cm-1. Four serum pools prepared at the Centers for Disease Control were analyzed on each of 15 days. Within-run variation of the protein values (expressed as CV) in the eight laboratories ranged from 0.1 to 2.5% and day-to-day (total) variation in six of the laboratories ranged from 0.4 to 1%.

Biuret Reaction↗
PubMed1978

Laboratory standardizatin in an international study: the Kaunas--Rotterdam intervention study (KRIS).

Laboratory results obtained in different laboratories over lengthy periods of time usually are difficult to compare. In cooperative long-term studies where such results must be pooled, thorough standardization of methods is vital. We describe a program in which comparable plasma cholesterol and glucose analyses have been obtained, by simple methods. In the Netherlands and the Soviet Union in close collaboration with the Center for Disease Control, Atlanta, Ga., U.S.A. The two laboratories produced glucose values (direct o-toluidine reaction) within 2% of the target reference values and cholesterol results (direct Liebermann-Burchard reaction) with a consistent 6-8% positive bias over the reference method values. Intralaboratory precision was subject to preset acceptance limits. The use of common control materials, exchange of patient samples, and on-site comparison of all details of laboratory procedures are vital tools in standardization efforts. A laboratory protocol that included quality requirements and rejection criteria was developed and proved to be indispensable. The experience gained should be useful in standardizing inter-laboratory results in similar studies.

Blood Glucose↗