Alexithymic asthmatics: the miscommunication of affective and somatic states.
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Biomedical subjects
Publications and source records attributed to E L Brown.
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Signal detection theory predicts a square root 2 recognition memory performance advantage for the two-alternative forced choice (2AFC) procedure over the yes-no (YN) procedure. In auditory psychophysics this advantage has been related to greater demands on memory in the YN task. The present experiment tested this prediction by assessing face-recognition accuracy and confidence in 72 college student subjects. Testing method (2AFC or YN) and encoding instructions (standard, overall gestalt, or distinctive feature scan) were varied, the latter in an effort to vary trace strength to see whether stronger traces would yield a lesser 2AFC advantage. A 1-week retention test revealed an overall 2AFC advantage of 1.61 and superiority of gestalt and feature-scan instructions over standard ones. While confidence and accuracy were related both within and across subjects, 2AFC subjects were significantly more confident than YN ones. Intriguingly, more efficient encodings resulted in a greater, rather than a lesser 2AFC advantage.
Respiratory failure due to an exacerbation of chronic obstructive airways disease is often seen by clinicians. A case in which respiratory failure was further complicated by acute hypophosphataemia is reported. Replacement phosphate therapy resulted in a dramatic improvement in the clinical condition of the patient. The aetiology of the hypophosphataemia was thought to be a combination of acidosis, and the administration of corticosteroids, 5% dextrose and antacids. It is suggested that hypophosphataemia may account in part for the poor prognosis associated with severe exacerbations of chronic obstructive airways disease.
Certain patient styles perpetuate chronic physical illness, defeat medical treatment, and increase the utilization of medical services. Two such extreme styles among asthmatic patients are indexed by the MMPI panic-fear scale, reflecting either (a) helpless dependency and anxiety, or (b) excessive inappropriate independence. The present findings indicate that both of these patient styles are related to excessively high hospitalization rates during the two 1-year periods after discharge from intensive treatment, even among patient groups having asthma of similar objective severity. The discussion centres upon the increased demand for medical services, and the need for early identification of patients whose personal styles contribute to the maintenance of illness.
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The total synthesis of a tyrosine suppressor tRNA gene with a modified promoter is described. The alteration involves the replacement of the four G:C base pairs immediately preceding the start point of transcription by A:T base pairs. The new sequence contains the recognition sequence for the HindIII restriction endonuclease at the transcriptional start point, thus permitting fusion of the structural gene with promoters containing independent sequence modifications. The construction, cloning, and biological activity of several recombinant DNAs containing the tRNA gene with the modified promoter are described. The expression of this gene in vivo is compared with that of both the unmodified synthetic suppressor gene and a naturally occurring tyr su3+ gene cloned onto a multicopy plasmid.
Chemical syntheses of two tridecanucleotides, d(G-C-A-T-C-A-T-A-T-C-A-A-A) and d(G-C-G-T-C-A-T-T-T-G-A-T-A), and three undecanucleotides, d(G-G-A-A-G-C-G-G-G-G-C), d(T-G-A-T-G-C-G-C-C-C-C), and d(T-G-A-C-G-C-G-C-C-G-C), are described. These deoxyribo-oligonucleotide segments together represent the DNA duplex corresponding to the previously determined nucleotide sequence -1 to -29 of the promoter region of the tyrosine tRNA gene (Sekiya, T., van Ormondt, H., and Khorana, H.G. (1975) J. Biol. Chem. 250, 1087-1098). Chemical syntheses used the principles of stepwise addition of protected mono- and oligonucleotides to the 3'-hydroxyl end of growing oligonucleotide chains. The desired condensation products were isolated by solvent extraction methods in the case of di- and trincleotides and by anion exchange chromatography in the case of longer chains. All the five synthetic oligonucleotides were characterized by chromatographic and radioactive fingerprinting methods after labeling at the 5'-ends with a [32P]phosphate group.
The total synthesis of a 207-base pair-long DNA, which is biologically functional as a tyrosine suppressor transfer RNA gene, has been completed. The synthesis involved the enzymatic joining of the previously synthesized duplexes. Thus, the duplex corresponding to the promoter region [P] (Sekiya, T., Brown, E.L., Ramamoorthy, B., Fritz, H.-J., Gait, M.J., Lees, R.G., Ryan, M.J., Khorana, H.G., and Norris, K.E. (1979) J. Biol. Chem. 254, 5781-5786) was jointed to Duplex [I] (Caruthers, M.H., Kleppe, R., Kleppe, K., and Khorana, H.G. (1976) J. Biol Chem. 251, 658-666) to form [P + I]. Separatively, Duplex [III + IV + Vb] was prepared from the previously described Duplexes [III], [IV], and [Vb]. (Loewen, P.C., Miller, R.C., Panet, A., Sekiya, T., and Khorana, H.G. (1976) J. Biol. Chem. 251, 642-650; Sekiya, T., Besmer, P., Takeya, T., and Khorana, H.G. 1976) J. Biol. Chem. 251, 634-641; Ramamoorthy, B., Lees, R.G., Kleid, D., and Khorana, H.G., (1976) J. Biol Chem. 251, 676-694). The product [P + I], was joined to Duplex [II] (Panet, A., Kleppe, R., Kleppe, K., and Khorana, H.G. (1976) J. Biol. Chem. 251, 651-657) and then to [III + IV + Vb] without isolation of the intermediates. In all the above joinings, the duplexes carried 32P-labeled phosphate groups at the appropriate 5'-ends. The total DNA and the intermediate duplexes were all characterized by their relative mobilities in electrophoresis on polyacrylamide gel slabs, by nearest neighbor analysis, and by degradation to 5'-nucleotides of radioactively labeled joined products. Two succeeding papers describe the transcription in vitro and the suppressor activity in vivo, of the synthetic gene now described.
Chemical syntheses of the two dodecanucleotides d(T-C-A-A-C-G-T-A-A-C-A-C) and d(A-C-G-T-T-G-A-G-A-A-A-G), the two undecanucleotides d(T-T-T-A-C-A-G-C-G-G-C) and d(T-G-T-A-A-A-G-T-G-T-T), the decanucleotide d(A-G-T-C-C-G-A-A-A-G), and the nonanucleotide d(A-A-T-T-C-T-T-T-C) are described. These deoxyribo-oligonucleotide segments, excluding the decanucleotide, represent the DNA duplex corresponding to the previously determined nucleotide sequence -30 to -51 of the promoter region of the gene for the tyrosine suppressor tRNA (Sekiya, T., Gait, M.J., Norris, K., Ramamoorthy, B., and Khorana, H.G. (1976) J. Biol. Chem. 251, 4481-4489) and include the EcoRI restriction endonuclease sequence at the appropriate 5'-end. The nona- and decanucleotide along with the previously synthesized deoxyribo-oligonucleotide segments 25 to 27 (Ramamoorthy, B., Lees, R.G., Kleid, D., and Khorana, H.G. (1976) J. Biol. Chem. 251, 676-694) together represent the DNA duplex corresponding to the natural nucleotide sequence 121 to 142 of the region adjoining the C-C-A end of the tyrosine tRNA gene and, in addition, a run of nine nucleotides which include the EcoRI restriction enzyme sequence at the 5'-end. The syntheses used protected mono- and oligonucleotides and stepwise condensation methods. A noteworthy feature of the present syntheses was the use of reverse phase high pressure liquid chromatography for the rapid and efficient separation of synthetic reaction mixtures.
By use of polynucleotide kinase and polynucleotide ligase, the 10 deoxyoligonucleotide segments, whose syntheses have been described in accompanying papers, have been joined to form the 62-nucleotide-long DNA corresponding to the promoter region of an Escherichia coli suppressor tRNA gene. The following sequence in the joining reactions was used to obtain error-free and optimal yields of the products: 1) joining of Segment P-1 to P-3 in the presence of Segment P-2; 2) joining of Segments P-4 to P-7 to form Duplex [P4-7]; 3) joining of Segments P-8 to P-10 to Duplex [P4-7] to form Duplex [P4-10]; and finally, 4) joining of P-(1 + 3) and P-2 to Duplex [P4-10] to form the total promoter Duplex [P].
The chemically synthesized gene for Escherichia coli tyrosine suppressor tRNA has been joined to both plasmid (ColE1 ampr) and bacteriophage (Charon 3A) vector chromosomes after the latter had been digested with the restriction endonuclease EcoRI. Suppression of both bacterial (trpA, his, lacZ) and bacteriophage lambda amber mutations (Aam32, Bam1) has been demonstrated after transformation of E. coli with the recombinant DNA molecules carrying the synthetic suppressor tRNA gene. The cloned synthetic gene has been reisolated from the vector chromosomes after digestion of the latter with EcoRI restriction endonuclease and characterized in regard to its size and its ability to serve as a source of suppressor activity in further transformation experiments. This synthetic gene has also been shown to suppress bacterial amber mutations after it had been incorporated into the E. coli chromosome as part of a lambda prophage. Transcription, in vitro, of the cloned synthetic suppressor gene gave a product which, on treatment with a crude E. coli extract, afforded the tyrosine suppressor tRNA precursor. The latter was characterized by two-dimensional fingerprinting after digestion with T1-RNase. Exposure of the in vitro transcript to RNase P Selectively released the 41-nucleotide-long fragment characteristic of the 5'-end of the tRNA precursor. Thus, the nucleotide sequence of the cloned gene is accurate and its expression is controlled by its promoter.
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Reverse phase high-pressure liquid chromatography (HPLC) using columns containing microparticulate materials with bonded octadecyl groups has been developed as a rapid and efficient method for the separation of nucleosides, nucleotides, and, in particular, of protected oligonucleotides which are standard intermediates in the stepwise synthesis of deoxyribopolynucleotides. Reported are extensive studies of the influence of the different purine and pyrimidine bases, of protecting groups, of the phosphate groups, and of the chain lengths of oligonucleotides on their retention on such columns. Further, the application of HPLC in the stepwise synthesis of an oligonucleotide, d(G-G-A-A-G-C-T-T-A-A-C), has been described. The methods, which are herein described, lend themselves to separations on a preparative scale and effect a marked reduction (up to 50%) in the time required for the synthesis of oligonucleotides.
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A group of U.S. scientists engaged in inflight measurements of pilot workload discussed the problems and aspects of workload; the techniques used for inflight measurements; the various workload models, such as design-oriented, operational, psychological, and physiological concepts; different experimental approaches; and experiences, results and further plans, during the 48th Annual Scientific Meeting of the Aerospace Medical Association in Las Vegas, Nv, on May 10, 1977. The contributions by the chairman and the five panel members are summarized.