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Biomedical subjects

A Adams

Publications and source records attributed to A Adams.

At least 145 records · Page 8Linked to original sources
PubMed1985

Interaction of DNA-intercalating antitumor agents with adrenoceptors.

The interaction between some examples of mononuclear and binuclear DNA-intercalating antitumor agents and alpha- and beta-adrenoceptors has been studied using radioligand-binding assays. Competition for 125I-BE 2254, [3H]rauwolscine, and (-)-[3H]dihydroalprenolol binding was used to assess affinity for alpha 1-, alpha 2-, and beta-adrenoceptor-binding sites, respectively. Two homologous series of alkyl-linked diacridines and diquinolines were found to interact poorly with beta-adrenoceptors, with only the largest members having appreciable affinity. By contrast, these compounds bind strongly and in a complex manner to alpha 1- and alpha 2-adrenoceptors. The affinity of diacridines for both alpha-adrenoceptor classes has a parabolic dependence on alkyl chain length with the hexyl and pentyl derivatives being the most potent at the alpha 1- (Ki = 11.5 +/- 2.3 nM) and alpha 2- (Ki = 143 +/- 26 nM) binding sites, respectively. The dependence of inhibition constants on linker chain length for the diquinolines is more complicated, with the ethyl- and heptyl-linked dimers having the greatest affinity for each alpha subclass. There is a nadir in affinity for the pentyl and butyl ligands and an increase in dissociation constant for octyl and longer homologues. Thus, the ethyl diquinoline has Ki values of 6.6 +/- 1.2 and 110 +/- 14 nM for the alpha 1- and alpha 2- adrenoceptors, respectively, and, correspondingly, the heptyl derivative has values of 39 +/- 4 and 51 +/- 1 nM. These findings are discussed with respect to a model of the alpha-adrenoceptor in which the radioligand-binding site is situated in a trench or cleft, surrounded by a flat surface bounded by walls. Daunomycin was found to have no affinity for adrenoceptors of any type and mitoxantrone similarly fails to interact with alpha 2- and beta-adrenoceptors, but binds to the alpha 1 subclass with an inhibition constant (Ki) of 3930 +/- 420 nM. Bisantrene also has no affinity for beta-adrenoceptors but binds to alpha 1- and alpha 2- adrenoceptors with Ki values of 145 +/- 24 and 2310 +/- 430 nM, respectively. Among the mononuclear acridine drugs studied, only nitracrine shows detectable interaction with beta-adrenoceptors (Ki = 760 +/- 50 nM). This compound, like bisantrene, has high affinity for the alpha 1-adrenoceptor (Ki = 131 +/- 17 nM) and moderate affinity for the alpha 2 subclass (Ki = 2180 +/- 500 nM).(ABSTRACT TRUNCATED AT 400 WORDS)

Acridines↗
PubMed1985

Symposium on infections in the compromised host. External barriers to infection.

Knowledge of the external barriers to infection is the first step in understanding the normal defense mechanisms of the host. The intact skin and mucous membranes, with their normal flora and secretions, the action of cilia in the upper respiratory tract, secretory functions, and the normal flow of body fluids are all important factors associated with the external defense against infections. When these barriers are altered or breached, the potential for infection increases and the internal immune system is activated to assist in defending the body.

Bacterial Infections↗
PubMed1984

Deafferentation of the rat hippocampus does not alter the affinity or binding capacity for the alpha 1-adrenoceptor radioligand [125I]BE 2254.

Sectioning the dorsal afferents to the rat hippocampus led to an 88% decrease in the level of noradrenaline in the dorsal third of the structure, a 62% reduction in the medial region and no significant change in the ventral third. The lesion did not produce a change in either the affinity or maximum binding capacity of the alpha 1-adrenoceptors in any of the three regions of the hippocampus, as assessed by the binding of the radioligand [125I]BE 2254. This result indicates that reported increases in the response to noradrenaline in hippocampal slices after denervation is most likely due to a loss of noradrenaline uptake mechanisms.

Afferent Pathways↗
PubMed1984

Imitation and social responsiveness in autistic children.

Fifteen autistic children, ages 4-6 years, participated in the present study. Imitation and object permanence skills were assessed. Language and social behaviors were observed during free play. Children were also exposed to three interactive procedures that differed in developmental sophistication. The experimenter either (1) simultaneously imitated the child's actions, (2) modeled a familiar action, or (3) modeled a novel action. It was found that the autistic children who had a low level of imitative ability (Piaget's Stages 2-3) were more socially responsive, showed more eye contact, and played with toys in a less perseverative manner when the experimenter imitated their behavior than when the experimenter modeled either a familiar or a novel action. When the experimenter modeled a familiar as opposed to a novel action, these children were more likely to spontaneously imitate the experimenter. The autistic children with more highly developed imitation skills, however, responded similarly to all conditions. They also were generally more socially and verbally responsive. These results suggest that developmental status is an important variable in designing intervention programs for severely impaired children.

Age Factors↗
PubMed1984

The role of self-produced movement and visual tracking in infant spatial orientation.

In two longitudinal studies, infants were trained at 12 and 18 months to find an object hidden in one of two identical wells in a Plexiglas box. On the test trial, normal access was blocked and infants were either guided by their mother or allowed to move on their own to another opening on the opposite side. In Experiment 1 significantly more correct responding occurred after active movement than after passive at 12 months, with correct responding related to high visual tracking. In contrast, at 18 months correct search without tracking predominated among both movement conditions. A difference between the conditions in the position of the mother on the test trial was ruled out as a contributor to performance on the basis of data from Experiment 2. When opaque sides were inserted to prevent tracking in Experiment 3, active movement no longer facilitated correct search at 12 months, thus indicating that the tracking and not the active movement per se was the critical factor.

Attention↗
PubMed1984

A new PGE1 analogue (CL115,574) III. Effects on gastric acid and mucus secretion in man.

CL115,574, an analogue of PGE1, is a potent inhibitor of gastric acid secretion in animals. The effects of this compound on gastric acid and mucus secretion were studied in 8 male volunteers. The compound was well tolerated, and its maximally effective antisecretory dose (750 micrograms) inhibited pentagastrin stimulated acid secretion by approximately 40% over a 2-hour period, with stimulation beginning one hour after the drug was orally administered. CL115,574 proved to have a significant and sustained effect upon the stimulation of mucus secretion into gastric juice. Considering the possible role that mucus may play in mucosal cytoprotection, CL115,574 because of its antisecretory and mucogenic actions may prove to be an important clinical anti-ulcer compound.

Adult↗
PubMed1984

Biochemical diagnosis of type 1b glycogen storage disease.

A child with the classical signs and symptoms of Type 1 glycogen storage disease is presented, who on investigation was shown to have a recently described variant of this disease known as Type 1b glycogen storage disease. A reliable and simple procedure for the diagnosis and differentiation of Types 1 and 1b glycogen storage disease is described, as the conventional diagnostic approach of assaying glucose-6-phosphate phosphohydrolase in frozen tissue will not diagnose Type 1b glycogen storage disease. A portion of biopsy tissue should be maintained at a temperature near 0 degrees C (but not frozen) and the remainder frozen. Glucose-6-phosphate phosphohydrolase assays are carried out on the tissue homogenates of both portions. In Type 1 glycogen storage disease, glucose-6-phosphate phosphohydrolase activity will be low or absent in both frozen and unfrozen tissues. In Type 1b glycogen storage disease the frozen tissue homogenate will exhibit normal glucose-6-phosphate phosphohydrolase activity due to the disruption of the microsomes by ice crystals, while in the unfrozen tissue low levels of glucose-6-phosphate phosphohydrolase activity will be detected.

Clinical Enzyme Tests↗
PubMed1984

Electron microscopic evidence for replication of circular Epstein-Barr virus genomes in latently infected Raji cells.

Raji cells, collected at various times from a synchronized culture, were gently lysed, and the high-molecular-weight DNA was enriched ca. 10-fold for latent Epstein-Barr virus (EBV) genomes by equilibrium density gradient centrifugation in neutral CsCl. The heavy-density DNA pool, which included more than 90% of the total intracellular EBV DNA sequences, was further fractionated by velocity sedimentation on neutral glycerol gradients, and material from fractions containing potential EBV DNA replicative forms was examined in the electron microscope. Early in the cellular S phase, when the EBV DNA content was found to be doubling in parallel with host chromosome replication, half of the 50- to 55-micron circular EBV genomes were observed to have two or more DNA branch points or forks. Most molecules were in a relaxed theta configuration, indicative of the Cairns mode of DNA replication. In the supercoiled state, the two daughter strands of the partially replicated molecules were seen to be wrapped around each other. Two theta structures had more than two DNA forks, indicating that DNA replication can initiate more than once on the same DNA molecule. Late in the S phase, the EBV DNA sedimenting at positions where theta structures were found with early S phase samples was composed of catenated dimers rather than partially replicated genomes. It is concluded that the circular EBV genomes, which are the major intracellular form in latently infected cells, are maintained as independent replicons and are not synthesized from an integrated template.

Burkitt Lymphoma↗
PubMed1983

Preparation and properties of a complex from rat liver of polyribosomes with components of the cytoskeleton.

Gel filtration with 1% agarose (Bio-Gel A-150m) separates polyribosomes bound to microsomal membranes from 'free' polyribosomes when these fractions are prepared by standard centrifugal techniques. However, when polyribosomes contained in an unfractionated postmitochondrial supernatant are run on an identical column, over 90% of the total polyribosomes are present as aggregates, designated 'membrane-cytomatrix', which are eluted in the column void volume. Polyribosomes are not released from these aggregates on removal of microsomal phospholipids by treatment of postmitochondrial supernatant with 1% Triton X-100, a neutral detergent. The aggregates are disrupted by the usual ultracentrifugation techniques used in subcellular fractionation. After treatment of membrane-cytomatrix with Triton X-100 to remove phospholipids and membrane proteins, 58% of the polyribosomes still remain associated with protein-containing complexes in the form of a cytomatrix and are not 'free'. Preparations of both membrane-cytomatrix and cytomatrix are capable of sustained protein synthesis. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis revealed that the cytoskeletal proteins actin and myosin are present in the cytomatrix. Incubation of cytomatrix preparations with the actin-depolymerizing agent deoxyribonuclease I caused release of the polyribosomes. Polyribosome release by deoxyribonuclease I was prevented by prior incubation with phalloidin, which is known to stabilize F-actin. Thus polyribosomes are associated with cytoskeletal elements in rat liver, and this association is dependent on polymeric forms of actin.

Animals↗
PubMed1983

Measurement of osmolality and sodium concentration in heated-cup sweat collections for the investigation of cystic fibrosis.

A new system (Wescor) for sweat collection and analysis was examined with respect to its suitability for the investigation of children suspected to have cystic fibrosis. The effects of iontophoresis current, sweat collection time, sweat storage and analysis were examined, and as a result the technique was modified to allow collection and storage of sufficient sweat for sodium and potassium as well as osmolality assays in 10-20 minutes. The small electrodes and speed of the procedure make it practical for use with small children, with a reproducibility of 13-24% (coefficient of variation for whole procedure).

Adult↗
PubMed1982

Gallbladder disease in pregnancy.

Cholecystosonography was performed on 338 obstetric patients, and the gallbladder was successfully visualized in 93% of them. Gallbladder volume increased with duration of pregnancy. Three and one-half percent of the patients had obvious cholelithiasis, and a total of 4.2% had abnormalities. These findings suggest that cholecystosonography should become part of the routine obstetric ultrasound examination.

Adolescent↗
PubMed1982

Lack of alpha-adrenoreceptor binding of [125I]BE2254 to rat basilar artery membranes.

Rat basilar arteries do not contain classical alpha- or beta-adrenoreceptors as assessed by electrophysiological techniques even though these arteries are innervated by catecholamine-containing perivascular nerves. These arteries were therefore examined for their ability to selectively bind an alpha-adrenoceptor radioligand, [125I]BE2254 (2/beta/4-hydroxyphenyl)-ethylaminomethyl)-tetralone). For comparison, rat tail arteries were also studied as these are known to contain functional alpha-adrenoreceptors. It was found that basilar artery membranes had only one-third of the specific binding of tail artery membranes and this finding collaborates the electrophysiological data.

Animals↗
PubMed1982

Development of a radioiodinated ligand for characterising alpha 1-adrenoceptors.

Two alpha-adrenoceptor antagonists, phentolamine and 2-(beta-(4-hydroxyphenyl)-ethylaminomethyl)-tetralone (BE 2254) which are phenolic derivatives were radioiodinated after chloramine-T oxidation of Na125I and the labelled material isolated by chromatography. 125I-phentolamine does not bind selectively to alpha-adrenoceptors in guinea pig brain whereas the 125I-BE 2254 derivative binds rapidly, reversibly and with high affinity to these receptors with a Kd of 230 pM. At low concentrations of 125I-BE 2254 (less than 100 pM) approx. 90% of the bound radioligand is specifically bound and under these conditions drug displacement studies show that the ligand binds predominantly to the alpha 1 subclass of adrenoceptors. Binding measurements to kidney and smooth muscle membrane preparations indicate that 125I-BE 2254 may also be a useful tool in the study of alpha-adrenoceptors in peripheral tissues. The high specific activity of 125I-BE 2254 permits the use of minimal quantities of membrane material for receptor assay and ligand displacement measurements, e.g. 250 micrograms per assay tube, and this provides a significant advantage over the use of existing radioligands such as 3H-prazosin which requires approx. 40 times as much tissue.

Animals↗
PubMed1982

Establishment and characterization of a human EBV-negative B cell line (MN 60).

A permanent cell line, MN 60, was established from the peripheral blood of a patient with an acute lymphoblastic leukemia (ALL) classified morphologically as being of the L3 type. Cell growth started rapidly in vitro and no feeder cells were needed. Cells of the MN-60 line were identical to the original leukemic cells with respect to surface immunoglobulin (Ig) expression and karyotype, including the presence of four marker chromosomes [1q+, 6q-, t(8;14)]. Continuous proliferation was maintained in stationary suspension culture with a doubling time of 25 h. The cells were tumorigenic in athymic nude mice and had the capacity to form colonies in semi-solid medium in vitro. Monoclonal surface Ig (mu lambda) was demonstrated whereas no cytoplasmic immunoglobulin could be demonstrated. The MN-60 cells were Epstein-Barr virus (EBV) negative as evidenced by EBNA tests and by nucleic acid hybridization studies. The cells expressed HLA-A-C, HLA-DR. beta 2-Microglobulin and cALL, but not Fc gamma. C3, sheep and mouse red blood cell receptors. No reactivity was found with anti-glycophorin A or the anti-BL 38.13 monoclonal antibody. Cell growth was retarded in the G0/G1 phase of the cell cycle after incubation with leukocyte interferon, hydrocortisone, phorbol myristate acetate and dimethyl sulphoxide.

Adult↗