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Biomedical subjects

A Mann

Publications and source records attributed to A Mann.

At least 163 records · Page 9Linked to original sources
PubMed1990

The Gospel Oak Project: the use of health and social services by dependent elderly people in the community.

The Gospel Oak Project surveyed a community sample of elderly people. Prevalence rates of depression and dementia were determined. Cases were assessed in detail and subject to long-term follow-up. Demographic information and morbidity data identified details of health service, social service and informal service contact. This paper reports the findings of the first survey of this population completed in 1987. It examines the effect of the increase in the very elderly on the need for health and social services, including contact with general practitioners. Duplication of service contacts are explored and the dependent elderly people not in receipt of services are identified. Finally, the survey investigates the effect of informal care on the level of service contact. Results confirm that contact increases with age, especially multiple service contact, implying a need for an expansion in future services. Although most depressed residents do not usually complain of depression, they have increased contact with health services but are not treated with anti-depressant medication. Few dependent elderly people receive no services; conversely there is no evidence of service duplication. Finally, receipt of informal care affected attendance at a day centre but no other service provision.

Aged↗
PubMed1989

Inhibition of cyclic adenosine-3',5'-monophosphate phosphodiesterase from vascular smooth muscle by rolipram analogues.

Rolipram [(R,S)-4-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-pyrrolidone] has been shown to inhibit selectively the cAMP phosphodiesterase (PDE) of vascular smooth muscle. In order to further explore the structural requirements for selective PDE inhibition, we synthesized a series of rolipram derivatives differently substituted either at the pyrrolidinone or at the aromatic ring. Among these compounds, rolipram was the most active compound. Semirigid analogues were prepared and used for an evaluation of the active conformation of rolipram. Structural comparison with two other potent and chemically different smooth muscle cAMP-PDE inhibitors, trequinsin and Ro 20-1724, allows us to propose a first topological model of the smooth muscle cAMP-PDE pharmacophore.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1988

Structural relationships between clathrin assembly proteins from the Golgi and the plasma membrane.

We have established by peptide mapping and immunochemical analysis of purified clathrin assembly protein preparations from bovine brain, that the cluster of components of mol. wt 100-120 kd fall into four classes, which we term alpha, beta, beta' and gamma. The beta and beta' proteins are immunologically related and generate a series of common tryptic peptides. The same criteria reveal no such homologies between the alpha, beta(beta') and gamma polypeptides. The so-called HA-II assembly protein group contains equimolar amounts of alpha and beta class polypeptides, which are shown to interact with each other. In the HA-I group assembly protein complex gamma and beta' class polypeptides form a stoichiometric complex. Immunofluorescence microscopy reveals that the HA-I complex is specifically associated with clathrin-coated membranes in the Golgi region of cultured cells, whereas the HA-II complex appears to be restricted to coated pits on the plasma membrane. The data lead to the tentative conclusion that the clathrin assembly proteins are involved in the recognition of the intracellular targets by uncoated vesicles.

Animals↗
PubMed1988

Abnormal eating attitudes in London schoolgirls--a prospective epidemiological study: factors associated with abnormal response on screening questionnaires.

One thousand and ten unselected London state schoolgirls were screened by questionnaire to identify an 'at risk' cohort displaying abnormal eating attitudes and two control cohorts, one with probable general psychiatric morbidity, one without. Members of all cohorts were assessed at interview for the presence of eating disorder and for putative risk factors implicated in the development of anorexia nervosa. A prevalence rate of 0.99% was detected for clinical eating disorder and 1.78% for the partial syndrome of eating disorder. Factors specifically associated with abnormal eating attitudes were identified, in particular, current or past overweight, history of amenorrhoea and perceived stress in school and social life. Some commonly accepted risk factors for eating disorders were discovered to be associations with general psychiatric morbidity. These were perceived parental pressure to eat more, taking exercise to lose weight, perceived stress at home and reporting a family history of anxiety or depression. Other well reported putative risk factors for eating disorder, including social class, birth order, age at menarche, obsessional personality and weight related career choice were not associated specifically with abnormal eating attitudes in schoolgirls. These findings represent cross-sectional data at entry into a prospective epidemiological study.

Adolescent↗
PubMed1988

RNA is covalently linked to SV40 large T antigen.

RNA is shown to be covalently linked to the large tumor antigen (TAg) of simian virus 40 (SV40). Proteolytic digestion of TAg, isolated in the presence of ribonuclease inhibitors from SV40 transformed Balb/c mouse cells, generated a specific phosphopeptide of high charge heterogeneity that was strongly retained on DEAE-cellulose in the presence of 7 M urea. Hydrolysis of this peptide with RNAase released the four standard ribonucleotide monophosphates. Analysis of peptide digestion products showed that the RNA is attached to TAg through a phosphodiester linkage between the beta-hydroxyl of a serine and the 5' phosphate of an invariant cytidine residue. The methods applied to SV40 TAg can be applied to other proteins, including cellular oncogene products, to investigate the possibility of covalent protein-RNA interactions.

Antigens, Polyomavirus Transforming↗
PubMed1986

Induction of experimental allergic neuritis in the BN rat: P2 protein-specific T cells overcome resistance to actively induced disease.

T lymphocyte lines specific for the peripheral nerve myelin protein P2 were selected from the lymph nodes of Brown Norway (BN) rats immunized with bovine P2 protein in complete Freund's adjuvant. These T cells expressed the W3/25+, OX8-phenotype and responded specifically to bovine P2 protein, but not to PPD or bovine basic protein, in T cell proliferation assays. When injected i.v. into syngeneic recipients, BN P2-specific T cell lines induced both clinical and histologic signs of experimental allergic neuritis (EAN), overcoming the resistance of this rat strain to actively induced EAN. Although the histopathology of the disease was indistinguishable from that seen in T cell-mediated EAN in the Lewis rat, disease onset was considerably later, 7 to 8 days after cell transfer, as opposed to 4 days in Lewis. This lag phase between inoculation and disease onset could not be further reduced even by raising the cell dose to 50 X 10(6) cells/host. The fine specificity of the T cell response to P2 differs between Lewis- and BN-derived T cell lines. At least one neuritogenic epitope for each strain was present in the cyanogen bromide-derived peptide CB2 (residues 21-113), as shown by the ability of CB2-specific T cell lines derived from each strain to transfer EAN to the appropriate host strain. However, neuritogenic BN T lines fail to mount a response to the sequence 53-78 (SP4), which encompasses an epitope that is neuritogenic for Lewis rats. These results demonstrate that the resistance of BN rats to actively induced EAN is not due to the lack of appropriate P2-specific autoreactive T cell clones in the normal T repertoire. Furthermore, the results suggest that two distinct epitopes of P2 are responsible for EAN in Lewis and BN rats.

Animals↗
PubMed1986

Effects of phthalic acid esters on the liver and thyroid.

The effects, over periods from 3 days to 9 months of administration, of diets containing di-2-ethylhexyl phthalate are very similar to those observed in rats administered diets containing hypolipidemic drugs such as clofibrate. Changes occur in a characteristic order commencing with alterations in the distribution of lipid within the liver, quickly followed by proliferation of hepatic peroxisomes and induction of the specialized P-450 isoenzyme(s) catalyzing omega oxidation of fatty acids. There follows a phase of mild liver damage indicated by induction of glucose-6-phosphatase activity and a loss of glycogen, eventually leading to the formation of enlarged lysosomes through autophagy and the accumulation of lipofuscin. Associated changes are found in the kidney and thyroid. The renal changes are limited to the proximal convoluted tubules and are generally similar to changes found in the liver. The effects on the thyroid are more marked. Although the levels of thyroxine in plasma fail to about half normal values, serum triiodothyronine remains close to normal values while the appearance of the thyroid varies, very marked hyperactivity being noted 7 days after commencement of treatment, this is less marked at 14 days, but even after 9 months treatment there is clear cut evidence for hyperactivity with colloid changes which indicate this has persisted for some time. Straight chain analogs of di-2-ethylhexyl phthalate, di-n-hexyl phthalate and di-n-oxtyl phthalate differ entirely in their short-term effects on the liver and kidney but have similar effects on the thyroid. The short-term in vivo hepatic effects of the three phthalate esters can be reproduced in hepatocytes in tissue culture. All three phthalate esters, as well as clofibrate, have early marked effects on the metabolism of fatty acids in isolated hepatocytes. The nature of these changes is such as to increase storage of lipid in the liver. A hypothesis is presented to explain the progress from these initial metabolic effects to the final formation of liver tumors.

Animals↗
PubMed1985

Photoaffinity labeling of D-2 dopamine binding subunits from rat striatum, anterior pituitary and olfactory bulb with a new probe, [3H]azidosulpride.

A novel photoaffinity probe [3H] azidosulpride has been developed for biochemical studies of D-2 dopamine receptors. This ligand binds to the receptors with high affinity (Kd = 3.1 +/- 0.2 nM) and, upon photoactivation, about 20% of the radioactivity bound to membranes becomes covalently incorporated. More than 90% of this irreversible binding is protectable by dopaminergic agents including D-2 selective compounds, whereas D-1 selective and non-dopaminergic compounds are ineffective. Analysis by sodium dodecylsulfate polyacrylamide gel electrophoresis reveals a single band at Mr = 85 kDa for labeled receptors in striatum, anterior pituitary or olfactory bulb, where pharmacologically distinct binding sites have been previously detected.

Affinity Labels↗
PubMed1985

The use of [3H](-)-DO 710 as selective dopaminergic ligand for binding and autoradiographic studies.

DO 710, a benzamide derivative previously shown to display a dopamine antagonistic potency superior to that of sulpiride, was 3H-labeled. Its use as radioligand was assessed in membrane binding and autoradiographic studies. The compound displayed relatively high affinity (Kd 2 nM) and pronounced selectivity for dopamine receptors (distinct from D-1 receptors) as well as low non-specific binding particularly evidenced in autoradiographic experiments. Hence [3H](-)-DO 710 displays distinct technical advantages over commonly used dopaminergic radioligands.

Animals↗
PubMed1985

Synthesis and activity of 5-(aminomethylene)-1,3-cyclohexanediones: enolic analogues of gamma-aminobutyric acid.

Eight 1,3-cyclohexanediones with an aminoalkyl side chain in the 5-position were synthesized as rigid enolic analogues of GABA (gamma-aminobutyric acid). Biochemical investigations about their abilities to displace [3H]GABA and [3H]baclofen [beta-(p-chlorophenyl)-gamma-aminobutyric acid] in binding studies or to inhibit the high-affinity sodium-dependent GABA uptake showed that these compounds were generally devoid of affinity for the two GABA receptors and for the GABA carrier. Only compound 1 exhibited a weak affinity in the GABA-A binding experiments (IC50 = 6.5 X 10(-5) M). Graphic computer modeling was applied in an attempt to explain this activity in comparison to some reference GABA agonists. Electrophysiological studies on dorsal root ganglia (DRG) also excluded agonistic or antagonistic properties on GABA-A or GABA-B receptor models but pointed out an atypical prolongation of Ca2+-dependent action potential for compound 1.

Action Potentials↗
PubMed1985

Plasma protein changes in rats treated with hypolipidaemic drugs and with phthalate esters.

Treatment of rats with hypolipidaemic drugs or with the plasticizer di-2-ethyl hexyl phthalate caused significant alterations in the concentration of certain plasma proteins. Certain proteins showed dose-dependent increases, in other cases the plasma concentrations fell in treated animals. The changes were quite distinct from the changes in plasma proteins which occur during the acute-phase response to inflammatory agents. Some changes appeared specific to agents which produce peroxisome proliferation in liver, other alterations appeared associated with mild, but sustained, liver injury.

Animals↗