Psychiatric symptoms and low blood pressure.
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Fatigue↗
Biomedical subjects
A Mann
Publications and source records attributed to A Mann.
Sequence differences between HLA-B and TNF distinguish different MHC ancestral haplotypes.
The HLA-B locus is extremely polymorphic. We have sequenced a region, CL, telomeric of HLA-B that also shows a high degree of allelic variation which we have shown previously by RFLP analysis. The polymorphism can be accounted for by sequence variation in duplicated, reiterated sequence elements called geometric elements. Comparison of the CL1 and CL2 sequences from the 57.1, 8.1, 18.2 and 7.1 ancestral haplotypes revealed that the lengths of the elements vary, both between the duplicated loci within a haplotype and between haplotypes, apparently because certain sequences are inserted or deleted. It is possible, using the polymerase chain reaction, to amplify these elements in genomic DNA from ancestral haplotypes for which sequence data of the CL region are not available and to obtain gel patterns which are characteristic of different ancestral haplotypes. The most striking feature of the data is the fact that the majority of the CL patterns are haplospecific; i.e. have a particular pattern that is unique for a particular ancestral haplotype and can be used to type these ancestral haplotypes. At least 12 different allelic patterns have been identified within a panel of 29 cell lines representing 16 ancestral haplotypes. For these 16 ancestral haplotypes, all examples of each haplotype have the same CL pattern. The haplotypic nature of the patterns confirms that ancestral haplotypes are conserved chromosomal segments and that coding and non-coding sequences are identical by descent from a remote ancestor.
Base Sequence↗
Aerobic exercise in the adjunctive treatment of depression: a randomized controlled trial.
Two clinical trials have been conducted in a sample of depressed patients to determine whether the addition of an aerobic exercise programme to their usual treatment improved outcome after 12 weeks. In the first trial, an aerobic exercise group had a superior outcome compared with a control group in terms of trait anxiety and a standard psychiatric interview. A second trial was then conducted to compare an aerobic exercise programme with low intensity exercise. Both groups showed improvement but there were no significant differences between the groups. In neither trial was there any correlation between the extent of change in the subjects' physical fitness due to aerobic exercise and the extent of the improvement of psychiatric scores.
Adult↗
Recent advances in lipoprotein metabolism and the genetic dyslipoproteinemias.
The elucidation of the structure and function of the plasma apolipoproteins has provided the unique opportunity to understand the physiological pathways for the transport and cellular metabolism of the plasma lipoproteins. The complexity of the individual density classes of plasma lipoproteins has been revealed by a detailed analysis of the apolipoprotein composition of the individual lipoprotein particles. In addition, the elucidation of the molecular defects in patients with dyslipoproteinemias has now permitted the understanding of the defects at the level of the apolipoprotein gene. The ability to define the genetic defect in individuals at risk for the development of premature cardiovascular disease provides the unique opportunity to now identify these individuals at an earlier age, and to initiate therapy to prevent the development of early heart disease.
Apolipoprotein A-I↗
Synthesis and biochemical evaluation of baclofen analogues locked in the baclofen solid-state conformation.
The synthesis of six close analogues of baclofen [3-(4-chlorophenyl)-4-aminobutyric acid] (BAC), a potent GABAB agonist, are reported. The compounds were designed starting from the structural informations contained in the solid state of BAC, regarded as a possible bioactive conformation, in which the p-chlorophenyl ring is perpendicular to the GABA backbone. A similar conformational situation was created by rigidifying the BAC structure by means of methylene (1), ethylene (2 and 6), or propylene (3) units, or by introducing chlorine atoms (4 and 5) into the ortho positions ("ortho effect"). Only compound 5 showed affinity for the GABAB receptor. Compound 6 [1-(aminomethyl)-5-chloro-2,3-dihydro-1H-indene-1-acetic acid], which was initially considered as representing the optimal mimic of the solid-state conformation of BAC, was surprisingly found inactive. An extensive conformational analysis was performed on compounds 1-6 in order to evaluate their flexibility and the overlap of their conformational population with respect to BAC. For this purpose a distance map was generated from three possible pharmacophoric groups: the amino and the carboxylic functions, and the phenyl ring. Finally, several explanations are proposed to account for the poor affinities of the prepared compounds such as steric hindrance or flexibility demand of the receptor.
Animals↗
Tired, weak, or in need of rest: fatigue among general practice attenders.
OBJECTIVES: To determine the prevalence and associations of symptoms of fatigue. DESIGN: Questionnaire survey. SETTING: London general practice. PARTICIPANTS: 611 General practice attenders. MAIN OUTCOME MEASURES: Scores on a fatigue questionnaire and reasons given for fatigue. RESULTS: 10.2% Of men (17/167) and 10.6% of women (47/444) had substantial fatigue for one month or more. Age, occupation, and marital status exerted minor effects. Subjects attributed fatigue equally to physical and non-physical causes. Physical ill health, including viral infection, was associated with more severe fatigue. Women rather than men blamed family responsibilities for their fatigue. The profile of persistent fatigue did not differ from that of short duration. Only one person met criteria for the chronic fatigue syndrome. CONCLUSIONS: Fatigue is a common complaint among general practice attenders and can be severe. Patients may attribute this to physical, psychological, and social stress.
Adult↗
Optically active benzamides as predictive tools for mapping the dopamine D2 receptor.
Substituent variations on the pyrrolidinyl nitrogen of sulpiride, a selective D2 dopamine antagonist, showed that in vitro and in vivo activities are concentrated in the (S) optical series for N-alkyl analogs and in the (R) series for N-benzyl analogs. To account for these unusual structure-activity relationships, a pharmacophoric model was built from the crystallographic structure of (-)piquindone and extended to 14 other D2 antagonists. This model considers the lone pair orientation of the basic nitrogen rather than its spatial location. Two distinct active conformations for benzamides were defined, corresponding to the (S) and (R) series. An extended pharmacophore is then proposed involving four main anchoring areas: (i) an aromatic site Ar1, (ii) a tertiary nitrogen with its lone pair orthogonal to the Ar1 plane, (iii) a dipole delta 1 coplanar to the Ar1 ring and (iv) three sites for the N-substituent, including a small hydrophobic pocket and two different aromatic binding sites Ar2 and Ar3. To probe the predictive value of this model, structures were designed and several compounds were synthesized and tested as inhibitors of [125I]iodo-sulpiride binding to rat striatal membranes and as antagonists of apomorphine-induced stereotyped behavior in mice.
Animals↗
Analysis of 100-180-kDa phosphoproteins in clathrin-coated vesicles from bovine brain.
Protein kinases which co-purify with clathrin-coated vesicles are known to phosphorylate in vitro the 50-kDa subunit of the HA-II adaptor complex and upon inclusion of polylysine the beta-light chain of clathrin and polypeptides above 100 kDa. Here we relate the high molecular mass phosphoproteins to the known subunits of the adaptor protein complexes and to other clathrin-associated proteins by means of immunoprecipitation with monoclonal antibodies, two-dimensional electrophoresis, or electrophoresis in urea-sodium dodecyl sulfate-polyacrylamide gels. Our results show that some of the labeling of the 100-120-kDa region is accounted for by the beta'- and gamma-subunits of the HA-I adaptor complex, the alpha a-, and, to a lesser extent, by the beta-subunits of the HA-II adaptor complex. In addition, we found the assembly protein AP 180 and a hitherto undescribed 110-kDa coat polypeptide to be heavily phosphorylated upon release of these proteins from the coated vesicle membrane. In all cases, labeling was confined to serine residues.
Amino Acids↗
The Gospel Oak Study: prevalence rates of dementia, depression and activity limitation among elderly residents in inner London.
The steps to setting up a population register of elderly residents are described. Based upon this, 87.2% of the elderly residents of an inner-city electoral area were screened for memory disorder, depression and activity limitation using the Short CARE. Contact with medical and social agencies was also recorded; 4.7% were classed as cases by the dementia diagnostic scale, sufferers being older and not living alone. Of the residents 15.9% were classed as depressed, this state being more prevalent in those not currently married. The depressed were, in contrast to the demented residents, likely to be in recent contact with hospital and general practitioner. Thirty-two per cent of the population showed impairment in daily activity, these individuals were usually older, not married and receiving hospital care. Sleep disorder and complaint of many somatic symptoms were associated with a diagnosis of depression. In contrast, most respondents with a subjective complaint of memory disorder, which was common in this population, were neither suffering from depression nor dementia. With this accurate sampling frame and a good response rate, the prevalence rate of clinical depression must be seen as disturbingly high. The prevalence rate of dementia approximated to that of other surveys. This study also indicated that general practitioners' lists may be inaccurate and that non-responders to first approaches for interview, although similar in demographic features to those responding, may contain among them many suffering from dementia.
Activities of Daily Living↗
The Gospel Oak Study stage II: the diagnosis of dementia in the community.
An attempt was made to assess in detail subjects screened as suffering from dementia among a North London community sample of elderly people. Forty-eight (80%) subjects were interviewed, 7 (12%) were found to have died and 5 (8%) either refused interview or were lost to follow-up. By clinicians' diagnosis of the 48 interviewed, 22 subjects (46%) had probable Alzheimer's disease, one had multi-infarct dementia, five had mixed dementia, five had secondary dementia, 10 had a dementia which could not be further classified and 5 were not demented. No subject had a reversible condition. The prevalence rate for clinical dementia was 6.1%, and for Alzheimer's disease 3.1%. According to AGECAT diagnosis the prevalence of organicity was 5.7%. The AGECAT diagnoses and psychiatrists' diagnoses were significantly associated (P less than 0.003) and AGECAT was more likely to identify as organic those subjects with dementia diagnosed by psychiatrists as Alzheimer's disease, than those not so diagnosed (P less than 0.04). A short psychometric battery, including the MMSE in two versions, was administered and its acceptability to a community sample evaluated. This detailed clinical investigation showed that the Dementia Diagnostic Scale of the Short-CARE was a specific predictor of clinical dementia or death at the time of follow-up, whereas the more inclusive Organic Brain Syndrome scale was a more satisfactory first phase screening instrument.
Aged↗
Use of the ICD-10 version of the Standardized Assessment of Personality to determine the prevalence of personality disorder in psychiatric in-patients.
The Standardized Assessment of Personality (SAP) involves a short semi-structured interview with an informant. It was modified to accord with the 1987 draft of the tenth revision of the International Classification of Diseases (ICD-10) and used to assess the pre-morbid personality of first-admission patients in one London area over the period of one year. Of the 120 (84% of the total sample of first-admissions) patients included, 43 (36%) were found to satisfy the ICD-10 criteria for personality disorder and a further 17 (14%) to satisfy the criteria for personality trait accentuation.
Adult↗
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↗
The nature of Taung dental maturation.
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Animals↗
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↗
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↗
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↗
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↗