PubMed HealthSearch

Biomedical subjects

F Wright

Publications and source records attributed to F Wright.

At least 19 recordsLinked to original sources

Codon usage in the G+C-rich Streptomyces genome.

The codon usage (CU) patterns of 64 genes from the Gram+ prokaryotic genus Streptomyces were analysed. Despite the extremely high overall G+C content of the Streptomyces genome (estimated at 0.74), individual genes varied in G+C content from 0.610 to 0.797, and had third codon position G+C contents (GC3s) that varied from 0.764 to 0.983. The variation in GC3s explains a significant proportion of the variation in CU patterns. This is consistent with an evolutionary model of the Streptomyces genome where biased mutation pressure has led to a high average G+C content with random variation about the mean, although the variation observed is greater than that expected from a simple binomial model. The only gene in the sample that can be confidently predicted to be highly expressed, EF-Tu of Streptomyces coelicolor A3(2) (GC3s = 0.927), shows a preference for a third position C in several of the four codon families, and for CGY and GGY for Arg and Gly codons, respectively (Y = pyrimidine); similar CU patterns are found in highly expressed genes of the G+C-rich Micrococcus luteus genome. It thus appears that codon usage in Streptomyces is determined predominantly by mutation bias, with weak translational selection operating only in highly expressed genes. We discuss the possible consequences of the extreme codon bias of Streptomyces and consider how it may have evolved. A set of CU tables is provided for use with computer programs that locate protein-coding regions.

Base Composition

Isochromosome 1q in acute monocytic leukemia: a new nonrandom association.

We report a case of de novo acute monocytic leukemia in a 25-year-old man in whom the sole clonal cytogenetic abnormality was an additional isochromosome 1q. Cytogenetic polymorphisms indicate that, in addition to the formation of the isochromosome, a duplication of the remaining normal chromosome 1 had taken place. Other reported cases suggest an association between acute monocytic leukemia and i(1q).

Adult

A 2359-base pair DNA fragment from Cryptosporidium parvum encoding a repetitive oocyst protein.

A Cryptosporidium parvum lambda gt11 expression library was constructed using EcoRI-digested genomic DNA extracted from in vitro-excysted oocysts. Screening of this library with rat anti-Cryptosporidium antiserum led to the isolation of a clone containing a 2359-bp EcoRI fragment. When this fragment was ligated into the EcoRI site of plasmid vector pMS1S, the resulting clone expressed a 200-kDa beta-galactosidase fusion protein. Western blot analysis using serum raised against this fusion protein indicated that the EcoRI fragment represented part of a gene encoding a 190-kDa oocyst wall protein of C. parvum. Sequencing of the fragment revealed a continuous open reading frame encoding 786 amino acids. The DNA sequence is relatively low in G+C (39.1%), and the third codon position contains only 17.9% G+C. The deduced peptide sequence has unusually high proportions of cysteine, proline, glutamine and histidine. Another striking feature of the amino acid sequence is the presence of distinctly repetitive regions based on conserved cysteine residues.

Amino Acid Sequence

Isoelectric focusing and 2D electrophoresis of the human androgen receptor.

Nuclear androgen receptors from cultured genital skin fibroblasts were analyzed by non-denaturing isoelectric focusing (IEF) in ultrathin polyacrylamide gels before and after photoaffinity labeling with [3H]methyltrienolone. Both reversibly and covalently labeled receptors focused at pH 5.28 +/- 0.20 when extracted from nuclei with high salt. Lowering of the salt concentration yielded, in both cases, a second species which focused at pH 7.16. This species became predominant when nuclei were sonicated in IEF sample buffer containing no salt, even after extensive nucleic acid digestion. Low salt cytosols from both prostate and foreskin focused as a single peak of pI: 4.93 +/- 0.31 which remained unchanged when KCl was added to the cytosol up to a concentration of 0.6 M. SDS-polyacrylamide gel electrophoresis of photoaffinity labeled receptors revealed labeled proteins with Mw 90-95 kDa. Two-dimensional electrophoresis of photoaffinity labeled nuclear receptors, extracted in low or high salt, showed that the two isoforms (pI 5.28 and 7.16) contain the same steroid-binding subunit with Mw 90-95 kDa. Nuclear receptors from 4 patients with the receptor positive form of the Complete Androgen Insensitivity Syndrome (CAIS, Rc+) were analyzed by non-denaturing IEF: a single species was observed, focusing at pH 6.0 whether in high or low salt conditions. These results indicate that the nuclear androgen receptor is an acidic protein with pI 5.28 and Mw 90-95 kDa under maximum protein dissociation conditions. When extracted under low salt conditions, it can be isolated in a neutral form (pI 7.16) suggesting its association with a nuclear protein. Receptors of (CAIS, Rc+) patients have an abnormal charge and show no pI shift upon lowering of the salt concentration suggesting that this shift could be a significant step in the mechanism of action of androgens.

Autoradiography

A crossover study of focused cognitive therapy for panic disorder.

OBJECTIVE: This study sought to determine the short- and long-term effects of focused cognitive therapy for panic disorder. METHOD: Thirty-three psychiatric outpatients with the DSM-III diagnosis of panic disorder were randomly assigned to either 12 weeks of individual, focused cognitive therapy or 8 weeks of brief supportive psychotherapy based on principles of client-centered therapy. The patients who received supportive psychotherapy were subsequently given the opportunity to cross over to cognitive therapy for 12 weeks. Patients were rated for panic and depression before therapy, after 4 and 8 weeks of therapy, and at 6-month and 1-year follow-up. RESULTS: Clinician ratings and self-ratings of panic frequency and intensity indicated that the focused cognitive therapy group achieved significantly greater reductions in panic symptoms and general anxiety after 8 weeks of treatment than did the group that received brief supportive psychotherapy. At 8 weeks, 71% of the cognitive therapy group were panic free, compared to 25% of the psychotherapy group. Moreover, 94% of the psychotherapy patients elected to cross over to 12 weeks of cognitive therapy. At 1-year follow-up, 87% of the group that received cognitive therapy only and 79% of the group that crossed over into cognitive therapy remained free of panic attacks. CONCLUSIONS: Focused cognitive therapy offers a promising nonpharmacological alternative for the treatment of panic disorder.

Adolescent

Needs of the family during critical illness of elderly patients.

Persons 65 years of age or older occupy 46% of all intensive-care beds. This number will rise in the next decade as the percentage of persons age 65 or older rises to a projected 13% by the turn of the century. Elderly patients require care that may be different from their younger counterparts. The needs of the families of the elderly may also be different. Nurses should carefully consider the needs and differences of each family, especially the need to participate in care and to be with the elder and the needs for information, reassurance, and comprehensive discharge planning.

Aged

[The estrogen-androgen profile is unchanged in men with cholelithiasis].

It is well established that cholelithiasis is more frequent in women than in men. This difference is usually explained by the effects of estrogens and progesterone on the metabolism of bile acids, biliary cholesterol secretion and saturation, and gallbladder motility. Another explanation could be a protective effect of androgens against cholelithiasis in men. To test this hypothesis, we determined the hormonal, androgenic and estrogenic, status of 15 male patients with asymptomatic gallstone disease and in 15 control patients with normal gallbladder matched for age and body weight. No significant difference in the plasma concentrations and the urinary excretion rate of sex hormones (testosterone, dihydrotestosterone, androstenedione, testosterone and androstanediol glucuronides, estradiol, estrone, total estrogens), as well as in the plasma sex hormone binding globulin, was found between the 2 groups of patients. The development of cholelithiasis in men, therefore, does not appear to be related to modification of sex steroids.

Adult

Symmetry of electro- and acoustic myographic activity of the lumbar paraspinal muscles in normal adults.

The symmetry of paraspinal muscle activity was examined in 15 healthy adults (aged 31-60 years). Acoustic myography (AMG), which provides a measure of force, was recorded with electromyography (EMG) to assess electromechanical relationships during contraction. Bilateral recordings of EMG and AMG were made over the paraspinal muscles at the level of the 4th lumbar vertebra during a fatiguing test manoeuvre. Subjects were strapped to a hinged couch in the prone position. When the upper part of the couch was lowered, subjects maintained the upper body (above the anterior, superior iliac spines) unsupported, in the horizontal position for 60 sec. The EMG and AMG signals were full-wave rectified, integrated (IEMG, IAMG) and recorded on an ink-jet oscillograph during the fatigue test. By 60 sec of activity, IEMG had increased (right 122% +/- 8.7; left 125% +/- 11.8; mean +/- 1 SD as a percentage of initial values) while IAMG (reflecting force) remained unaltered (right 99% +/- 8.2; left 100% +/- 5.3). The IAMG:IEMG ratio (reflecting efficiency of activation) thus declined (right 0.81 +/- 0.08; left 0.80 +/- 0.08). The similarly of changes on both sides of the spine have quantified normal symmetry of paraspinal muscle activity and could be used to assess asymmetry in patients with spinal pathology.

Acoustics

Selective venous catheterization in the evaluation of hyperandrogenism.

Retrograde bilateral ovarian-adrenal vein catheterization was carried out in 16 patients with plasma testosterone levels exceeding 1.4 ng/ml (4.85 nmol/l). While pelvic ultrasonography and computerized axial tomographic scan failed to locate the androgen-producing ovarian tumors, catheterization led to a diagnosis of occult ovarian tumor in 5 patients, based on the observation of an abnormally-high and unilateral ovarian-peripheral vein testosterone gradient, which was subsequently confirmed histopathologically. In one case, unilateral elevation of the adrenal-peripheral vein testosterone gradient was found, complementing the ultrasonographic finding of an adrenal mass and confirming the diagnosis of a virilizing adrenal tumor. In the other 10 patients, gradient analysis ruled out an androgen-producing tumor, leading to the identification of nontumoral hyperandrogeny, such as a severe form of the polycystic ovary syndrome in the 6 premenopausal patients and of ovarian stromal and hilus cell hyperplasia in the 4 menopausal patients. In conclusion, appropriate indication of selective catheterization may considerably reduce the need for exploratory surgery and may help in selecting the adequate surgical approach.

Adrenal Gland Neoplasms

The effects of the falling therapeutic and subtherapeutic barbiturate blood levels on electrocerebral silence in clinically brain-dead children.

In a retrospective study at a large children's hospital, we identified 92 children who had received barbiturates that were simultaneously discontinued at the time they were being evaluated for brain death in the presence of electrocerebral silence and clinical brain death by physical exam. Of these 92 children, 67 had barbiturate levels that were monitored from initial therapeutic or subtherapeutic levels. Repeat EEGs were obtained in 76 patients, and in all electrocerebral silence and clinical brain death (by exam) persisted despite the lower barbiturate levels. The study suggests that therapeutic and subtherapeutic barbiturate levels have no effect on the outcome of children who fulfill the criteria for brain death.

Adolescent

The role of the family as a support system for people with AIDS.

Family members, including family of origin and family of choice, are essential components of the PWA's support system. Family support is important in all high-risk groups, including gay men, IVDUs, and HIV-positive mothers and children. Before family members can be supportive, fear of infection and homophobia must be addressed. As the primary care provider, the NP can mobilize the resources to support family members, including emotional support from professionals and peers, education, and respite care.

Attitude to Health

The 'effective number of codons' used in a gene.

A simple measure is presented that quantifies how far the codon usage of a gene departs from equal usage of synonymous codons. This measure of synonymous codon usage bias, the 'effective number of codons used in a gene', Nc, can be easily calculated from codon usage data alone, and is independent of gene length and amino acid (aa) composition. Nc can take values from 20, in the case of extreme bias where one codon is exclusively used for each aa, to 61 when the use of alternative synonymous codons is equally likely. Nc thus provides an intuitively meaningful measure of the extent of codon preference in a gene. Codon usage patterns across genes can be investigated by the Nc-plot: a plot of Nc vs. G + C content at synonymous sites. Nc-plots are produced for Homo sapiens, Saccharomyces cerevisiae, Escherichia coli, Bacillus subtilis, Dictyostelium discoideum, and Drosophila melanogaster. A FORTRAN77 program written to calculate Nc is available on request.

Animals

Responses by general practitioners in Avon to proposals for general practice in the white paper Working for Patients.

OBJECTIVE: To determine the views of Avon's general practitioners about the general practice proposals within the government's white paper Working for Patients. DESIGN: Postal questionnaire survey. SETTING: A county in south west England. SUBJECTS: All general practitioner principals (n = 537) under contract with Avon Family Practitioner Committee. MEASUREMENTS AND MAIN RESULTS: 492 doctors (92%) responded to the survey. More than three quarters of the respondents were opposed to the government's proposals on budgets for specific surgical procedures, prescribing, and diagnostic tests; and between 63% and 93% felt negative about advantages that might accrue from the proposals. Over three quarters of general practitioners were in favour of family practitioner committees monitoring work load, prescribing, and referrals. General practitioners in large, potentially budget holding practices held similar views to doctors in smaller practices. CONCLUSIONS: Avon's general practitioners substantially reject most of the government's proposals about general practice in the white paper Working for Patients.

Attitude of Health Personnel

Androgen receptor in sexual differentiation.

Androgens play an essential role in sexual differentiation and their action is mediated by the androgen receptor (AR). The normal AR is a soluble protein, highly thermolabile, with a mol. wt of 90 kDa and a pI of 5.2 as determined by 2 dimensional (2D) gel electrophoresis. It is regulated by androgens in culture conditions but the physiological relevance of this regulation remains controversial. The presence of a functional AR is an absolute requirement for male sexual differentiation and its absence results in complete insensitivity. However, androgen insensitivity (complete or partial) can develop in the presence of a normal androgen binding capacity and there is no correlation between the clinical and the biochemical findings. A number of qualitative abnormalities have been described to explain the failure of androgen action in these cases: they all emphasize the extreme instability of the abnormal AR. It is difficult at the present time to determine whether these abnormalities result from structural mutations of the AR gene, transcriptional or post-transcriptional abnormalities. Further elucidation of these defects awaits for an antibody and/or a cDNA probe for the AR.

Animals

Increased thromboxane biosynthesis during coronary thrombolysis. Evidence that platelet activation and thromboxane A2 modulate the response to tissue-type plasminogen activator in vivo.

Platelet activation is markedly increased during coronary thrombolysis and limits the response to thrombolytic therapy. A possible mediator of platelet activation in this setting is thromboxane (TX) A2, a potent platelet agonist formed in greatly increased amounts during coronary thrombolysis in man. To address this hypothesis, we examined the role of TXA2 in modulating the response to intravenous tissue-type plasminogen activator (t-PA) in a chronic canine model of coronary thrombosis. Reperfusion occurred in 60 +/- 5 minutes and was complicated by spontaneous reocclusion. The times to reperfusion and reocclusion were platelet-dependent. Consistent with a role for TXA2 in this process, TXA2 biosynthesis, determined a excretion of its enzymatic metabolite, 2,3-dinor-TXB2, was markedly increased during coronary thrombolysis. Furthermore, inhibition of TXA2 by aspirin, given alone or in combination with a TXA2/prostaglandin endoperoxide receptor antagonist, accelerated reperfusion and partly inhibited cyclic flow variations during reperfusion. The delay in reperfusion and reocclusion induced by TXA2 appeared to be mediated by platelet aggregation since the F(ab')2 fragment of 7E3, a monoclonal antibody to the platelet GPIIb/IIIa, also accelerated reperfusion and prevented reocclusion without altering TXA2 biosynthesis. These finding suggest that platelet aggregation limits the response to coronary thrombolysis and that platelet activation in this setting is partly TXA2-dependent.

Angiography

The early natural history of subfoveal neovascular membranes in eyes with age-related macular degeneration.

During the course of age-related macular degeneration, the visual prognosis is abruptly changed when the presence of a subretinal neovascular membrane (SRNVM) is established by intravenous fluorescein angiography (IVFA). Patients who have been alerted to this condition may notice distortion on the Amsler grid and report within days of the onset of symptoms. Unfortunately most patients either do not notice the early changes in central vision or incorrectly attribute these symptoms to the development of cataracts and defer proper retinal evaluation for several months. We reviewed our records to determine the natural history of those SRNVMs which on initial IVFA either originated or extended into the foveal portion of the macula. Our results clearly indicate that treatment must be undertaken early in the course of this disease to maintain useful visual function for as long as possible.

Aged

Codon usage patterns in Escherichia coli, Bacillus subtilis, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Drosophila melanogaster and Homo sapiens; a review of the considerable within-species diversity.

The genetic code is degenerate, but alternative synonymous codons are generally not used with equal frequency. Since the pioneering work of Grantham's group it has been apparent that genes from one species often share similarities in codon frequency; under the "genome hypothesis" there is a species-specific pattern to codon usage. However, it has become clear that in most species there are also considerable differences among genes. Multivariate analyses have revealed that in each species so far examined there is a single major trend in codon usage among genes, usually from highly biased to more nearly even usage of synonymous codons. Thus, to represent the codon usage pattern of an organism it is not sufficient to sum over all genes as this conceals the underlying heterogeneity. Rather, it is necessary to describe the trend among genes seen in that species. We illustrate these trends for six species where codon usage has been examined in detail, by presenting the pooled codon usage for the 10% of genes at either end of the major trend. Closely-related organisms have similar patterns of codon usage, and so the six species in Table 1 are representative of wider groups. For example, with respect to codon usage, Salmonella typhimurium closely resembles E. coli, while all mammalian species so far examined (principally mouse, rat and cow) largely resemble humans.

Amino Acids

"Silent" sites in Drosophila genes are not neutral: evidence of selection among synonymous codons.

The patterns of synonymous codon usage in 91 Drosophila melanogaster genes have been examined. Codon usage varies strikingly among genes. This variation is associated with differences in G+C content at silent sites, but (unlike the situation in mammalian genes) these differences are not correlated with variation in intron base composition and so are not easily explicable in terms of mutational biases. Instead, those genes with high G+C content at silent sites, resulting from a strong "preference" for a particular subset of the codons that are mostly C-ending, appear to be the more highly expressed genes. This suggests that G+C content is reduced in sequences where selective constraints are weaker, as indeed seen in a pseudogene. These and other data discussed are consistent with the effects of translational selection among synonymous codons, as seen in unicellular organisms. The existence of selective constraints on silent substitutions, which may vary in strength among genes, has implications for the use of silent molecular clocks.

Animals