Biomedical subjects
Publications and source records attributed to J Owens.
Data from physical and genetic mapping studies show that the vegetative genome of the temperate, Group E 1 Salmonella bacteriophage, epsilon 15, is circularly-permuted. Preliminary evidence suggests that the circular permutation of the epsilon 15 genome is non-random.
This study investigates the prevalence of excessive drinking and alcohol-related problems amongst suicide attempts. It also compares the characteristics of attempted suicide by alcohol consumption group. Drinking histories were taken on 250 consecutive attempted suicides admitted to the West Midlands Poisons Unit. Fifty-one per cent of the men and 31% of the women drank more than the weekly limits recommended by the Health Education Council. Of the men, 22.5% drank more than 50 units of alcohol a week and 9.5% of the women drank more than 35 units of alcohol a week. Alcohol-related problems (social problems, alcohol dependence or physical illness) were present in 34% of men and 15.5% of women. These results show a greater incidence of alcohol misuse than previous studies on attempted suicide. This is probably because detailed alcohol histories were taken on all patients. Alcohol misuse is best treated before major alcohol-related problems develop. Those responsible for assessing cases of attempted suicide should be adept at detecting alcohol misuse and instituting appropriate management.
The op/op mouse, in which the M-CSF gene is mutated, has greatly reduced numbers of macrophages and osteoclasts. We assessed the ability of M-CSF to induce osteoclast and macrophage formation in op/op hemopoietic cells in vitro. Osteoclast production was undetectable in op/op cell cultures, but was restored by M-CSF at concentrations approximately an order of magnitude higher than those that induced macrophages. In normal hemopoietic tissue M-CSF similarly increased macrophage numbers, but inhibited osteoclast formation. Despite cure of the macrophage defect, neither interleukin 3 nor granulocyte-macrophage CSF were able to induce osteoclastic differentiation in op/op cells. The results suggest that M-CSF induces osteoclastic differentiation but that macrophages, which are also induced by M-CSF, suppress osteoclast differentiation. Macrophages induced by other cytokines seem unable to contribute to osteoclast-formation.
The Radiation Therapy Oncology Group in 1985 began a study of IORT plus external beam radiation therapy for patients with locally unresected, non-metastatic pancreatic cancer. Patients were treated with a combination of 2000 cGy of IORT and postoperative external beam radiation therapy to 5040 cGy in combination with IV 5-FU (500 mg/m2/day on the first 3 days of the external beam treatment). As patients were registered on study prior to exploration, it was expected that a number of patients would be excluded from further analysis at the time of surgery. Eighty-six patients were entered on study through 6/1/88 and analyzed through 4/90. Fifty-one patients were fully analyzable. Median survival time of the 51 patients was 9 months with an 18-month actuarial survival rate of 9%. Local control could not be adequately evaluated in this multi-institutional study. Major postoperative complications were not excessive and occurred in 12% of patients. Two patients had major late morbidity leading to death, one from duodenal bleeding and the second from biliary obstruction. Although this study does demonstrate the feasibility of IORT in a multi-institutional setting, it does not demonstrate any advantage of IORT over conventional therapy for this disease.
Quality assurance programs may significantly influence patient care by providing a systematic mechanism of self-assessment. An effective program should improve the level of care and have a positive effect on the fiscal base of a health care institution. The design of a useful quality assurance program is not a trivial matter. This report describes the details of a functioning quality assurance program developed for a multidisciplinary nutrition support service. The effect that such a program may have on patient care is also illustrated.
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Data were collected shedding light on the brain electrical activity underlying word recognition. Subjects listened to a list of 48 spoken words in six random orders under two instructional sets: first to "think about the meanings of the words," and second, to learn the list. The scalp EEG associated with hearing and identifying the words was recorded at F3, F4, Cz, P3, P4, Pz, and Oz. Standard within-subjects time-locked averaging across words showed a late negative-positive complex with N2-P3 topography, the negative component peaking around 480 msec, the positive component peaking around 830 msec. Averaging within words across subjects uncovered considerable latency variability in both components. Within-word N2 and P3 component latencies covaried with word durations and with the "recognition points" predicted for the words by the "cohort theory" of word recognition. N2 latencies corresponded closely to the "N400" effect elicited with semantically incongruous sentence-final spoken words. Implications for ERP investigations of language processing are discussed.
We measured local compositional complexity (LCC) of DNA sequences by calculating Shannon information content over mononucleotide frequencies. Eukaryotic DNA appeared to be "simpler" than bacterial DNA even at the level of short oligonucleotides. Moreover, different DNA functional domains displayed different compositional complexity in a systematic manner. In particular, the complexity of exon sequences was systematically higher than the complexity of corresponding introns. We therefore present examples of complexity charts (plots of complexity versus position in sequence) for pre-mRNA sequences from higher eukaryotes. By taking a window width of 100 nucleotides and a window step of 1 nucleotide, introns can be distinguished from exons in the majority of cases studied. Complexity charts of immunoglobulin variable regions allowed correct mapping of exons and introns in these sequences as well, a task that was impossible with commercial programs available to date.
Clinical and demographic factors associated with suicide attempts admitted to the West Midlands Poisons Unit over a 2-year period were compared by age group. Risk factors for future suicide (living alone, physical illness, psychiatric illness and high suicidal intent in the attempt) were significantly more common among elderly patients (65 years and over) than middle-aged patients (35-64 years) and significantly less common among young patients (under 35 years) than middle-aged patients. Elderly patients that attempted suicide resemble elderly patients that completed suicide and should be considered at high risk of future suicide.
A case of prolonged and refractory neuroleptic malignant syndrome was treated successfully with electroconvulsive therapy. Neuroleptic malignant syndrome and its treatment are reviewed.
A method for assessing the preserved stem-loops of RNA secondary structures is presented. Frequently recurring helical stems in a set of secondary structures resulting from the simulated folding process of a given RNA are assessed and consensus structural motifs can then be selected to construct a secondary structure of the RNA. Alternatively, it can be applied to a series of 'optimal' and 'suboptimal' secondary structures computed using the dynamic program developed by Williams and Tinoco. To demonstrate the power and the usefulness of the program we give examples of this procedure.
Prokaryotic promoters have been extensively studied to relate sequence features to promoter function. Here we examine the relationship between double-helix stability and promoter activity. The double-helix stability is evaluated from sequence data by free energy computation, based on reported values of dinucleotide free energies for strand separation. For a collection of 168 promoters, we find that within a 500-nucleotide span around the transcription initiation site the -10 region is the least stable. There is no correlation between the free energies and the rates of RNA polymerase-promoter open complex formation measured for 25 promoters. We also compare the free energies of 121 promoter mutations across the -35 and -10 consensus regions with the free energies of the corresponding wild-type sequences. These pairwise mutant-wild-type comparisons provide a particularly good test since the examined sequences differ only in one nucleotide so that all other sequence-dependent effects remain the same. About 80% of the mutations in the -10 region that show increased/reduced promoter activity are less/more stable than the wild types. The observed high free energy peak and the mutation data strongly support the conjecture that the instability, or melting properties, of the -10 region plays a significant role in promoter function.
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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.