Psychiatric illness among British Afro-Caribbeans.
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Biomedical subjects
Publications and source records attributed to J Owens.
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A fixed-point alignment analysis technique is presented which is designed to locate common sequence motifs in collections of proteins or nucleic acids. Initially a program aligns a collection of sequences by a common sequence pattern or known biological feature. The common pattern or feature (fixed-point) may be a user-specified sequence string or a known sequence position like mRNA start site, which may be taken directly from the annotated feature table of GenBank. Once all alignment markers are located, the sequences are scanned for occurrences of given oligomers within a specified span both upstream and downstream of the fixed-point. The occurrences may then be plotted as a function of the position relative to the fixed-point, displayed as an actual sequence alignment or selectively summarized via various program options. Applications of the technique are discussed.
Rates of deliberate self-poisoning in four immigrant groups, Asian, West Indian, Irish and Scottish were compared with those of English-born residents in an inner-city area of Birmingham. For both Asian and West Indian groups males and older females were underrepresented but young females had rates similar to the English group. Irish females and Scottish of both sexes were overrepresented. The rates of self-poisoning for all four immigrant groups considerably exceeded those of their country of origin, the difference being most marked among young Asian females. Explanations for these findings are examined.
A P450 gene nomenclature system has recently been proposed on the basis of divergent evolution of distinct families and subfamilies among eukaryotes and prokaryotes. At present, eleven gene families have been described, eight of which exist in all mammals. The current number of P450 genes in each species is believed to reflect, at least in part, selective advantages as animals and plants have struggled for coexistence during the last 1 billion years. It is likely that P450 genes will also be found in archaebacteria, as well as most or all eubacteria and eukaryotes. Using Wu-Kabat analysis, we propose regions of the P450 protein involved in membrane attachment, flavoprotein-binding, heme-binding, and substrate specificity. The invariant amino acid sequence (F**G***C*G in the heme-binding region) is unique to the fifty P450 proteins characterized to date and is not found in any of the more than 5,430 other proteins presently in the database. The regulatory trans-acting protein factors and their associated upstream cis-acting DNA elements of the orthologous mouse, rat and human P450A1 gene are complex but appear to be highly conserved during the 80 million years since the mammalian radiation.
To elucidate the mechanism of the t(14;18)(q32;q21) chromosomal translocation found in follicular lymphoma, we examined the structure of both derivative (der) chromosomal breakpoints as well as their germ-line predecessors. We noted that chromosome segment 18q21 was juxtaposed with immunoglobulin heavy (H) chain gene diversity (DH) regions on all five der(18) chromosomes we examined, and we confirmed the juncture with immunoglobulin H-chain gene joining (JH) regions on the der(14) chromosome. However, the t(14;18) was not fully reciprocal in that chromosome 14 DNA between the DH and JH regions was deleted. Furthermore, extra nucleotides, reminiscent of "N" segments, were present at the der(14) and possibly der(18) junctions. This indicates that despite the mature B-cell phenotype of follicular lymphoma, the t(14;18) occurs during attempted DH-JH joining, the earliest event in immunoglobulin rearrangement in a pre-B-cell. Our detailed analysis of the germ-line 18q21 region indicated that most breakpoints clustered within a 150-base-pair major breakpoint region. However, we found no evidence for evolutionarily conserved immunoglobulin-like recombinational signals at 18q21, arguing against a role for immunoglobulin recombinase in chromosome 18 breakage. Instead, a direct repeat duplication of chromosome 18 sequences was discovered at both chromosomal junctures, typical of the repair of a naturally occurring staggered double-stranded DNA break. These results prompt a translocation model with illegitimate pairing of a staggered double-stranded DNA break at 18q21 and an immunoglobulin endonuclease-mediated break at 14q32 and with N-segment addition, repair, and ligation to generate der(14) and der(18) chromosomes.
The characteristics of West Indian patients admitted to a Birmingham hospital following deliberate self-poisoning were compared with those of White self-poisoners. West Indian patients were more likely to be young, female and single. They were less likely to have previously self-poisoned, have received previous psychiatric treatment, or be suffering from a personality disorder or alcoholism, but were more often followed-up by a social worker. Rates of self-poisoning for those aged under 25 were similar but for those aged over 25 were lower for West Indians than Whites.
In eukaryotes, as in prokaryotes, evidence is accumulating showing that transcription factors recognize and bind to certain promoter elements. Sequence and chromatin structure perturbation specify the transcription initiation site and govern its efficiency. Two oligomers have been implicated in these processes: the TATAAATA and CCAAT. In the present work, all mammalian, non-mammalian vertebrate and invertebrate sequences accumulated in the database have been aligned by their mRNA start positions and scanned for recurrences of the 32 complementary triplets. The more significant signals are summarized here. In particular, TAT/ATA recurs very frequently further upstream, at -275, in addition to the 'classical' -40 position. Downstream their level is very low. The CAAT box complementary triplet components are not among the more striking signals. Closer examination of the -275 region indicates that to a large extent the signal is due to both the ATAT and the TATA quartets. Comparison of the frequencies of these quartets at -275 with the CAAT quartet at -80 suggests that the former signal is twice the strength of the latter. The oligomers' distribution charts support notions that several components are involved in recognition, making the regulatory regions more robust and less sensitive to mutations.
The characteristics of Asian patients admitted to a Birmingham hospital following deliberate self-poisoning were compared with those of British-born white self-poisoners. Asian patients were more likely to be young, female, and married. They were less likely to have previously self-poisoned, received previous psychiatric treatment, be diagnosed psychiatrically ill, or suffer from a personality disorder. Culture conflict was common among the Asian patients and was present in the majority of unmarried Asian females. The rate of self-poisoning for Asian females was higher than for white females, but for Asian males was lower than for white males.
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The effects of minimal acute liver injury on circulating ferritin levels have been examined in the rat both in vivo and in the isolated perfused liver. Liver damage produced by 6 mmol/kg of D-galactosamine (GalN) in vivo resulted in a marked rise in plasma ferritin levels 4 h after administration, 2 h before any significant increase in plasma aspartate transaminase. In the isolated perfused liver, damage produced by 5mM GalN introduced into the perfusate also produced an early increase in circulating ferritin before any evidence of release of intracellular enzymes, or alteration in liver histology as assessed by light microscopy was apparent. It is concluded that minimal acute liver damage results in a pronounced increase in circulating ferritin levels before other evidence of liver dysfunction. This is unlikely to be due solely to increased release from damaged cells but may rather result from an alteration in the mechanism responsible for ferritin homeostasis.
A monoclonal antibody JO1 X 1 was prepared against human abnormal prothrombin using the hybridoma technique. The clone secreting this antibody was selected on the basis of the ability of this antibody to bind to abnormal prothrombin, but not to prothrombin, in the presence of calcium ions. The antibodies were purified by affinity chromatography in EDTA on columns of prothrombin-Sepharose. Bound antibodies were eluted with 15 mM CaCl2. The kinetics of dissociation of antibody from the antibody-prothrombin complex with the addition of calcium ions fit a first-order kinetic model. Increasing CaCl2 concentration increased the rate of antibody-prothrombin dissociation. Ca(II) and Mn(II) inhibited antibody-prothrombin interaction; half-maximal binding was observed at 0.9 and 4 mM, respectively. Mg(II) had little effect on antibody-antigen interaction. The JO1 X 1 antibody bound fragment 1, fragment (1-39), abnormal prothrombin, and prothrombin equivalently in the presence of EDTA, but did not bind to des(1-44)prothrombin in the presence of EDTA or prothrombin in the presence of CaCl2. These results indicate that the monoclonal antibody JO1 X 1 is conformation specific for the calcium-free conformer of prothrombin and directed against an antigenic determinant near the NH2 terminus of prothrombin expressed in the 1-39 region of the protein. This analysis provides confirmation of the presence of a metal-free conformer of prothrombin.
The organization of the alpha- and beta-tubulin gene families in Physarum was investigated by Mendelian analysis. Restriction endonuclease-generated DNA fragments homologous to alpha- and beta-tubulin show length polymorphisms that can be used as markers for genetic mapping. Analysis of meiotic assortment among progeny of heterozygotes allowed alpha- and beta-tubulin sequence loci to be defined. There are four unlinked alpha-tubulin sequence loci (altA, altB, altC and altD) and at least three unlinked beta-tubulin sequence loci (betA, betB and betC). The alpha-tubulin loci are not linked to the beta-tubulin loci. --Segregation of tubulin sequence loci with respect to ben mutations that confer resistance to antitubulin benzimidazole drugs was used to investigate whether any members of the alpha- or beta-tubulin gene families are allelic to ben loci. The beta-tubulin sequence locus betB is allelic to the resistance locus benD, the betA locus is probably allelic to benA and the alpha-tubulin sequence locus altC may be allelic to benC. The molecular implications of benzimidazole resistance phenotypes when only one of the expressed beta-tubulin gene family members mutates to drug resistance are discussed in relation to tubulin function.
The DNAs of 17 isolates of varicella-zoster virus (VZV) were analysed by restriction endonuclease cleavage and agarose gel electrophoresis. By comparing gel patterns of DNAs cleaved with only a few enzymes, all epidemiologically distinct isolates were shown to be unique. Two isolates recovered from members of a family infected in a common-source outbreak were identical to each other (4/4 enzymes) but distinct from the other strains. In addition, three isolates recovered at different times during the course of a single episode of zoster in another individual were identical by endonuclease analysis (4/4 enzymes) but once again were distinct from all other isolates. The differences that have been recognized in cleavage profiles of all VZV strains reported thus far map into four regions of the viral genome. Two of these variable regions lie within the long unique sequences while the other differences appear to map in each of the inverted repeat sequences.
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Transluminal coronary angioplasty may be associated with complications resulting from the dilatation catheter and inflation of the balloon. The most common complications are dissection, occlusion, and coronary spasm. We report an unusual complication of coronary artery perforation by the dilatation catheter resulting in acute pericardial tamponade. The complication was immediately recognized and confirmed by dye injection and hemodynamic measurements. Pericardiocentesis was performed, followed by successful coronary bypass surgery. The reasons for the perforation are unclear. We postulate that the acute angle of the perforated vessel was an important factor for this complication. The importance of a standby cardiac surgeon and operating room is emphasized.
Varicella-zoster virus (VZV) DNA was cleaved with restriction endonuclease EcoRI, and most of the resulting fragments were successfully cloned in the phage vector lambda gtWES . lambda B. Double digestions of cloned fragments with EcoRI and BamHI and hybridizations to blot-transferred BamHI digests of VZV DNA were used to construct a physical map of the genome. The molecular termini of the DNA were identified by restriction enzyme analysis after exonuclease III digestion. The data indicate that VZV DNA exists in two isomeric forms that differ by inversion of one short terminal genome segment. Electron microscopic studies revealed that the short genome segment consists of a terminal revealed that the short genome segment consists of a terminal sequence of about 3.4 X 10(6) daltons that is separated from an internal inverted repeat of itself by a 5.8 X 10(60)-dalton unique DNA segment.
Varicella-zoster virus (VZV) DNA was prepared from nucleocapsids and from enveloped virions of a laboratory strain (Ellen) and directly from the vesicle fluids of patients with zoster infections. VZV Ellen nucleocapsid DNA was cleaved with 11 different restriction endonucleases and electrophoresed in agarose gels. The restriction profiles of the nucleocapsid DNA were identical to those of the DNA recovered from purified virions, but differed from those of another VZV strain (KM). In vitro-labeled VZV K.M. DNA purified directly from vesicle fluid yielded a distinct restriction pattern which appeared to be unchanged after several tissue culture passages of the isolate from that fluid. Restriction endonuclease analysis (EcoRI or BglII) of VZV DNA revealed the presence of four cleavage fragments with a molar ratio of approximately 0.5. No individual fragments with molar ratios of 0.25 were noted. This observation suggests that the VZV genome may contain one invertible segment. Comparison of the electrophoretic migrations of VZV DNA fragments relative to those of DNAs of known size permitted calculation of the VZV genome size to be 72 X 10(6) to 80 X 10(6) daltons. These results were confirmed by electron microscopy which demonstrated a genome size of about 76 X 10(6) daltons for passaged and unpassaged VZV DNA. Electron microscopy also revealed that some of the DNA molecules recovered from nucleocapsids or directly from vesicle fluids were superhelical circles.
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