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Biomedical subjects

S M Miller

Publications and source records attributed to S M Miller.

At least 145 records · Page 8Linked to original sources
PubMed1987

Electrophysiologic drug testing in symptomatic ventricular arrhythmias after repair of tetralogy of Fallot.

Nine patients with symptomatic ventricular arrhythmias were evaluated a mean interval of 16 years after surgical repair of tetralogy of Fallot. The clinical arrhythmia was sustained ventricular tachycardia (VT) in 4 patients (group I) and premature ventricular contractions in 5 (group II). All patients underwent cardiac catheterization and electrophysiologic studies. Ventricular tachycardia was induced at electrophysiologic study in all patients in group I and in 3 patients in group II. Six patients with inducible sustained monomorphic VT underwent chronic drug testing based on electrophysiologic study. A mean of 3.3 drugs per patient was tested. Patients with right ventricular systolic hypertension did not respond to any drug tested, and underwent surgery. Five patients received drug treatment based on the results of electrophysiologic study. During a mean follow-up period of 2.2 years, no patient in either group had recurrent episodes of VT or syncope. In the postoperative patient with tetralogy of Fallot with symptomatic ventricular arrhythmias, it is concluded that electrophysiologic study is useful in reproducing clinical episodes of VT and in selecting effective antiarrhythmic medication; a small number of patients with ventricular premature complexes alone will have inducible sustained VT during electrophysiologic study; prognosis of these patients may be improved by treatment that results in prevention of VT induction; and in patients with right ventricular hypertension, VT is likely to be refractory to drug treatment.

Adolescent↗
PubMed1987

Monitoring and blunting: validation of a questionnaire to assess styles of information seeking under threat.

Subjects were divided into information seekers (high monitors)/information avoiders (low monitors) and distractors (high blunters)/nondistractors (low blunters) on the basis of their scores on a self-report scale to measure coping styles, the Miller Behavioral Style Scale (MBSS). In Experiment 1, subjects were faced with a physically aversive event (the prospect of electric shock). High monitors and low blunters chose to seek out information about its nature and onset whereas low monitors and high blunters chose to distract themselves. This effect was strongest with the blunting dimension. High monitoring and low blunting were also accompanied by sustained high anxiety and arousal. In contrast, low monitors and high blunters were able to relax themselves over time. In Experiment 2, subjects worked on a series of tests that presumably predicted success in college. They could attend as often as they wished to a light that signaled how well they were performing. Results showed that coping-style scores accurately predicted informational strategy, particularly with the monitoring dimension: High monitors tended to look at the light whereas low monitors tended to ignore it. Thus the MBSS measure of coping styles appears to be a valid instrument for predicting behavioral strategies in response to both physical and psychological stressors. The theoretical and practical implications of these findings are discussed.

Adaptation, Psychological↗
PubMed1987

Directed mutagenesis in Candida albicans: one-step gene disruption to isolate ura3 mutants.

A method for introducing specific mutations into the diploid Candida albicans by one-step gene disruption and subsequent UV-induced recombination was developed. The cloned C. albicans URA3 gene was disrupted with the C. albicans ADE2 gene, and the linearized DNA was used for transformation of two ade2 mutants, SGY-129 and A81-Pu. Both an insertional inactivation of the URA3 gene and a disruption which results in a 4.0-kilobase deletion were made. Southern hybridization analyses demonstrated that the URA3 gene was disrupted on one of the chromosomal homologs in 15 of the 18 transformants analyzed. These analyses also revealed restriction site dimorphism of EcoRI at the URA3 locus which provides a unique marker to distinguish between chromosomal homologs. This enabled us to show that either homolog could be disrupted and that disrupted transformants of SGY-129 contained more than two copies of the URA3 locus. The A81-Pu transformants heterozygous for the ura3 mutations were rendered homozygous and Ura- by UV-induced recombination. The homozygosity of a deletion mutant and an insertion mutant was confirmed by Southern hybridization. Both mutants were transformed to Ura+ with plasmids containing the URA3 gene and in addition, were resistant to 5-fluoro-orotic acid, a characteristic of Saccharomyces cerevisiae ura3 mutants as well as of orotidine-5'-phosphate decarboxylase mutants of other organisms.

Candida albicans↗
PubMed1987

Development of autonomously replicating plasmids for Candida albicans.

A pool of Candida albicans RsaI fragments cloned onto a vector containing pBR322 sequences and the Candida ADE2 gene was used to transform a Candida ade2 mutant to adenine protrophy. A potential autonomously replicating sequence (ARS) in Candida DNA was identified by two criteria: instability of the selectable marker in the absence of selection and the presence of free plasmid in total DNA preparations. Plasmids carrying the ARS transformed C. albicans at a high frequency (200 to 1,000 ADE+ transformants per microgram of DNA), and Southern hybridization analysis of these transformants indicated that multiple copies of the plasmid sequences were present and that, although they were present in high-molecular-weight molecules, these sequences had not undergone rearrangement. Orthogonal field alternation gel electrophoresis indicated that the high-molecular-weight transforming sequences were not associated with any chromosome. The simplest interpretation to account for these data is that the transforming sequences are present as oligomers consisting of head-to-tail tandem repeats. The transformed strains occasionally yield stable segregants in which the transforming sequences are integrated into the chromosome as repeats. The Candida sequence responsible for the ARS phenotype was limited to a single 0.35-kilobase RsaI fragment which is present in one copy per haploid genome.

Candida albicans↗
PubMed1987

Race in the health of America.

Differentials in health and in effective access to health services cannot be considered apart from other dimensions of life, especially where public policy plays a large role. In some areas there has been progress, while in others discontinuities and inequities prevail. The toppling of overt barriers of racial segregation has not ensured active inclusion and full participation for many blacks. Among options for public strategy, a combined approach of consensus-building "universality" and efficient "targeting" may make for good policy and good politics.

Cultural Characteristics↗
PubMed1986

Cloning and characterization of the gene for rabbit C-reactive protein.

C-reactive protein (CRP), an acute-phase plasma protein of hepatic origin in man and rabbit, is a cyclic pentamer composed of five identical nonglycosylated Mr 22 500 subunits. We have isolated both cDNA and genomic clones for rabbit CRP. These clones were used as probes to demonstrate that when CRP synthesis is increased following an acute inflammatory stimulus, there is a corresponding increase in the level of accumulated CRP mRNA. The rabbit CRP gene is 2.6 kilobases in length containing a single intron of 252 base pairs (bp) which interrupts the codon for amino acid 2 in the protein. The mRNA for CRP contains a 5'-nontranslated region of 113 bp and a 3'-nontranslated region of 1550 bp. Sequencing of the protein-coding region of the gene indicates that the primary translation product contains a 20 amino acid N-terminal signal peptide. The deduced amino acid sequence is in general agreement with the published sequence [Wang, C. M., Nguyen, N. Y., Yonaha, K., Robey, F., & Liu, T.-Y. (1982) J. Biol. Chem. 257, 13610-13615] except in the region between amino acids 63 and 73. In this region, the sequence of both cDNA and genomic clones indicates the presence of 28 amino acids not previously reported. This alteration may be the result of genetic heterogeneity or an error in the reported protein sequence.

Amino Acid Sequence↗
PubMed1986

Two-electron reduced mercuric reductase binds Hg(II) to the active site dithiol but does not catalyze Hg(II) reduction.

Mercuric reductase contains FAD and a redox-active disulfide which is reduced to a thiol/thiolate pair in two-electron reduced enzyme (EH2) (Fox, B. and Walsh, C.T. (1982) J. Biol. Chem. 257, 2498-2503). A charge transfer interaction between the thiolate and oxidized FAD gives EH2 a characteristic absorption spectrum, very similar to that found with other flavoprotein disulfide oxidoreductases. We have examined the reaction of EH2 with HgCl2 (+/- mercaptoethanol) in stopped-flow kinetic and static titration experiments. In the absence of mercaptoethanol, reaction of EH2 with HgCl2 yields a final spectrum which is indistinguishable from that of oxidized enzyme. The nature of the final species was examined by titration of enzyme thiols with 5,5'-dithiobis-2,2'-nitrobenzoic acid under denaturing conditions in the presence of NaI to displace any Hg(II) bound to enzyme thiols. These studies demonstrate that EH2 tightly complexes Hg(II) with its active site thiols, but is incapable of reducing Hg(II) to Hg0. For the latter reaction to occur, additional reducing equivalents are required. In catalysis, the enzyme must first be reduced to EH2 after which it cycles between EH2 and EH2 X NADPH forms. This is in contrast to other flavoprotein disulfide oxidoreductases which cycle between Eox and EH2 forms in catalysis (Williams, C. H., Jr. (1976) in The Enzymes (Boyer, P. D., ed) 3rd Ed., Vol. 13, pp. 89-173, Academic Press, New York). With mercuric reductase, exogenous thiols are required for catalytic reduction of Hg(II) to Hg0. We have shown that this is due to prevention or reversal of formation of an abortive complex of Hg(II) with the thiol/thiolate pair of EH2.

Binding Sites↗
PubMed1986

Illness concerns and recovery from a URI.

Fifty ambulatory upper respiratory tract infection patients were studied to evaluate the nature of their illness concerns and explore the relationship between these concerns and subsequent recovery. Thirty-four patients still had URI-related symptoms 1 week after their medical visit, whereas 16 were asymptomatic. In general, asymptomatic patients could not be distinguished from symptomatic patients in terms of demographic variables, symptom type or duration, initial level of health concerns, physician findings, culture results, or therapy. Further, both groups exhibited surprisingly high levels of initial concern. Asymptomatic patients had a significantly greater reduction in these concerns shortly after their visit than the symptomatic group (P less than 0.01). Asymptomatic patients also reported more benefit from discussion of their concerns (P less than 0.01) and more satisfaction with this aspect of their care than the symptomatic group (P less than 0.001). The notion of illness concerns appears to be a concept worthy of clinical consideration and further investigation.

Adult↗
PubMed1986

Ventricular tachycardia in a young population without overt heart disease.

Since 1974, 24 young patients presenting with ventricular tachycardia and without clinical evidence of heart disease were evaluated and followed. Sixteen patients (67%) were symptomatic. Clinical episodes of ventricular tachycardia were sustained in 18, incessant in four, and nonsustained in two patients. The rate of tachycardia ranged from 130 to 300 beats/min (mean = 200 beats/min). Subtle abnormalities of cardiac size or function were present at cardiac catheterization in 16 of 23 patients (70%). During electrophysiologic studies, spontaneous ventricular tachycardia was present in six patients. The clinical ventricular tachycardia was inducible by programmed stimulation in 13 of 18 patients. The site of origin of tachycardia based on endocardial mapping in 17 patients was the right ventricle in 14, the ventricular septum in one, and indeterminate in two patients. Seventeen patients were treated based on results of short-term drug testing. During a mean follow-up period of 7.5 years, three patients died suddenly; none of these patients were receiving antiarrhythmic medication at the time of death. We conclude that in a young population without clinical evidence of heart disease, ventricular tachycardia may be the first manifestation of cardiomyopathy, since at least two-thirds of these patients have abnormalities at cardiac catheterization. Without treatment mortality in this population may be as high as 13% over an 8 year period. Presently we recommend treatment of ventricular tachycardia in any symptomatic patient, with therapy guided by electrophysiologic and treadmill testing. In addition, we recommend treatment for any asymptomatic patient with exercise-related tachycardia, since this group appears to be at increased risk for sudden death.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

[Significance and problems of Chlamydia detection in urologic patients].

Chlamydiae represent the aetiological agent in non-gonococcal urethritis in about 50% of the cases, but it is also increasingly recognized that Chlamydia trachomatis can cause prostatitis or epididymitis. The introduction of methods for the direct detection of chlamydia in clinical materials allows early diagnosis and therefore effective antibiotic therapy. The new tests however give both false positive and false negative results.

Antibodies, Monoclonal↗
PubMed1985

Secondary isotope effects and structure-reactivity correlations in the dopamine beta-monooxygenase reaction: evidence for a chemical mechanism.

The chemical mechanism of hydroxylation, catalyzed by dopamine beta-monooxygenase, has been explored with a combination of secondary kinetic isotope effects and structure-reactivity correlations. Measurement of primary and secondary isotope effects on Vmax/Km under conditions where the intrinsic primary hydrogen isotope effect is known allows calculation of the corresponding intrinsic secondary isotope effect. By this method we have obtained an alpha-deuterium isotope effect, Dk alpha = 1.19 +/- 0.06, with dopamine as substrate. The beta-deuterium isotope effect is indistinguishable from one. The large magnitude of Dk alpha, together with our previous determination of a near maximal primary deuterium isotope effect of 9.4-11, clearly indicates the occurrence of a stepwise process for C-H bond cleavage and C-O bond formation and hence the presence of a substrate-derived intermediate. To probe the nature of this intermediate, a structure-reactivity study was performed by using a series of para-substituted phenylethylamines. Deuterium isotope effects on Vmax and Vmax/Km parameters were determined for all of the substrates, allowing calculation of the rate constants for C-H bond cleavage and product dissociation and dissociation constants for amine and O2 loss from the enzyme-substrate ternary complex. Multiple regression analysis yielded an electronic effect of p = -1.5 for the C-H bond cleavage step, eliminating the possibility of a carbanion intermediate. A negative p value is consistent with formation of either a radical or a carbocation; however, a significantly better correlation is obtained with sigma p rather than sigma p+, implying formation of a radical intermediate via a polarized transition state. Additional effects determined from the regression analyses include steric effects on rate constants for substrate hydroxylation and product release and on KDamine, consistent with a sterically restricted binding site, and a positive electronic effect of p = 1.4 on product dissociation, ascribed to a loss of product from an enzyme-bound Cu(II)-alkoxide complex. These results lead us to propose a mechanism in which O-O homolysis [from a putative Cu(II)-OOH species] and C-H homolysis (from substrate) occur in a concerted fashion, circumventing the formation of a discrete, high energy oxygen species such as hydroxyl radical. The substrate and peroxide-derived radical intermediates thus formed undergo a recombination, kinetically limited by displacement of an intervening water molecule, to give the postulated Cu(II)-alkoxide product complex.

Copper↗
PubMed1985

Preference for control and the coronary-prone behavior pattern: "I'd rather do it myself".

We explored differential preference for control among Type A and Type B individuals. Forty-six subjects were threatened with an aversive event (loud noise) and were allowed to choose whether to turn off the noise themselves or to yield control to another (more competent) individual. The results showed that Type B subjects (regardless of sex) tended to relinquish control to their more competent confederates and thus reduce the aversive stimulus, whereas the choice behavior of Type As was less clear. In addition, although female subjects tended to yield control, male subjects were more inclined to retain it. Because the willingness to yield control in general appears to be stronger in women than in men, the behavior observed in Type As may be partly moderated by the subject's sex. Although there were suggestive trends in the data, the central psychological features of the Type A pattern remain ambiguous and await studies in which researchers explore these effects, using a variety of situations and larger sample sizes.

Arousal↗
PubMed1985

Restoration of the airway following bilateral recurrent laryngeal nerve paralysis.

Bilateral recurrent laryngeal nerve paralysis has been treated by a number of ingenious techniques that include arytenoidectomies, vocal cord lateralizations, cordectomies, and, recently, reinnervation procedures and laser arytenoidectomies. An arytenoidectomy is recommended by a thyrotomy approach without lateralization of the vocal cord. The resulting airway is adequate for decannulation by expansion of the posterior glottic aperture, with preservation of the anterior glottis for phonation.

Arytenoid Cartilage↗