Pharmacokinetics of gentamicin in Mammoth asses.
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Animals↗
Biomedical subjects
S M Miller
Publications and source records attributed to S M Miller.
Effects of coping style on psychological reactions of low-income, minority women to colposcopy.
Patterns of coping and adjustment in 36 low-income, minority women with positive cytologic smears were assessed prior to diagnostic follow-up examination (colposcopy). Subjects were divided into high monitors (who attend to threatening cues) and low monitors (who avoid threatening cues) on the basis of their scores on the Miller Behavioral Style Scale, a well-validated measure of coping style. Multivariate analysis of variance showed that high monitors worried more about the seriousness of their condition, expressed more concern about the immediate sensory and procedural aspects of the diagnostic examination and felt more responsible for the onset and course of their disease as compared to low monitors. However, they were no more likely to be concerned about the overall importance or long-term consequences of their abnormal smears. Finally, high monitors displayed greater symptoms of intrusive and avoidant ideation in relation to their medical status. These results were independent of sociodemographic and medical confounding variables. Consistent with results in other populations, the findings suggest that it may be useful to assess attentional coping dispositions in minority populations with high-risk gynecologic conditions and to target psychosocial interventions accordingly.
Adaptation, Psychological↗
Family physicians' support for school-based HIV prevention education programs.
OBJECTIVE: To identify the extent to which family physicians support school-based education programs regarding the human immunodeficiency virus (HIV). Sexually active adolescents are at risk for infection with HIV. Education programs on HIV that target this vulnerable group effectively prevent infection, yet family physicians are often not directly involved in the design and implementation of such programs. DESIGN: A systematic random sample of 2660 members of the American Academy of Family Physicians was surveyed using a mailed questionnaire to assess clinical experiences with HIV disease, willingness to provide HIV treatment, and support for school-based HIV education programs. The response rate was 63.7%. Poststratification weights were applied to adjust for the slight under-representation of non-board-certified physicians in the study sample. RESULTS: Support for school-based HIV counseling programs was overwhelmingly positive. The mean level of support was 1.28 (with 1 indicating strong approval and 4 strong disapproval). Physicians' attitudes toward programs that include condom availability were marginally less favorable (1.92). Residency trained (P = .009) and female physicians (P = .010) expressed the greatest support for school-based programs. Physicians with fewer professional concerns about providing direct HIV patient care (P = .030) and who believed that communication with their patients about sexuality was an acceptable component of clinical care (P < .001) were most likely to support school-based programs. CONCLUSIONS: Family physicians can play an important role in designing and implementing HIV education programs. The results of these analyses suggest family physicians may be relied on to endorse school-based HIV prevention programs, including programs that make condoms available to adolescents. School and public health authorities should enlist family physicians' assistance when planning and implementing these or related community-based HIV education activities.
Acquired Immunodeficiency Syndrome↗
Perceived controllability and the development of posttraumatic stress disorder (PTSD) in crime victims.
This study evaluated the association between perception of controllability and the development of posttraumatic stress disorder (PTSD) following criminal assault. Factor analysis of a perceived controllability scale revealed three factors; perceived controllability felt during the assault, expected controllability over future assaults, and perceived controllability over aversive events more generally. Only the latter factor was associated with PTSD symptom severity. The hypothesis that perceived controllability would be negatively associated with assault severity was partially supported. Further analyses showed that the association between controllability and PTSD was not mediated or moderated by assault severity measures. The role of perceived controllability in the development of PTSD is discussed.
Adaptation, Psychological↗
A comparison of DNA polymerase alpha from untransformed and SV40-transformed human fibroblasts.
1. DNA polymerase alpha (pol alpha) isolated from Simian virus 40 (SV40)-transformed cells showed more than 3-fold higher specific activity than pol alpha from normal cells. The enzymes from untransformed and transformed cells also differed in molecular size, thermolability, sensitivity to inhibitors and specificity of template-primer utilization. 2. Western analysis using anti-Tag to probe both a crude cell homogenate and partially purified pol alpha from SV40 transformed cells showed multiple immunoreactive bands with different molecular sizes. 3. While alpha polymerases from both normal and transformed cells exhibited tightly associated primase activity, they showed different DNA binding affinities. 4. These data suggest that T antigen binding to pol alpha alters the initiation of DNA replication and/or the function of pol alpha in SV40-transformed cells, and that pol alpha from SV40-transformed human fibroblasts have different catalytic subunit characteristics than pol alpha from untransformed cells.
Antigens, Polyomavirus Transforming↗
Jordan, an active Volvox transposable element similar to higher plant transposons.
We have isolated a 1595-bp transposable element from the multicellular green alga Volvox carteri following its insertion into the nitrate reductase (nitA) locus. This element, which we have named Jordan, has short (12-bp) terminal inverted repeats and creates a 3-bp target site duplication, like some higher plant transposons of the classic type. Contained within the first 200 bp of one end of the element are 55-bp inverted repeats, one of which begins with the terminal inverted repeat. Revertants of the transposon insertion into the nitA locus were obtained at a rate of approximately 10(-4) per Volvox embryo per generation. In each revertant examined, all transposon sequences were completely excised, but footprints containing both sets of duplicated bases, in addition to three to nine extra bases, were left behind. Jordan contains no significant open reading frames and so appears to be nonautonomous. DNA gel blot analysis indicates that Jordan is a member of a large family of homologous elements in the Volvox genome. We have isolated and characterized several of these homologs and found that they contain terminal very similar to those of Jordan. Efforts to utilize Jordan and its homologs as tools to tag and clone developmentally interesting genes of Volvox are discussed.
Base Sequence↗
Comparability of self-report of familial alcoholism among male and female college students.
There is a general impression in the literature that women are more accurate reporters of familial psychiatric history. In this regard, this study presents data from a large cohort of young men (n = 427) and women (n = 607) who in answering a questionnaire self-reported alcohol abuse symptoms for various biological relatives. No significant gender differences emerged for any of the family history comparisons including reports for father, mother, either parent, any first- or second-degree relatives, or men or women relatives. The findings are discussed in the context of the existing literature.
Adult↗
Comparison of recoveries from halothane vs isoflurane anesthesia in horses.
Recovery from isoflurane anesthesia was shorter, with no difference in quality, compared with halothane anesthesia in 2 groups of horses. In 1 group, 12 horses scheduled for elective arthroscopy were randomly assigned to receive halothane or isoflurane for maintenance of anesthesia during surgery. In the other group, 6 horses received anesthesia only, on 2 occasions, with halothane on 1 occasion, and isoflurane on the other. Difference in the quality of recovery was not seen between isoflurane and halothane anesthesia in either group. In the group that had surgery, recovery to sternal position was significantly shorter when isoflurane was used. In the group not treated surgically, recovery to sternal and standing positions was significantly shorter with isoflurane.
Acid-Base Equilibrium↗
C-terminal cysteines of Tn501 mercuric ion reductase.
Mercuric ion reductase (MerA) catalyzes the reduction of Hg(II) to Hg(0) as the last step in the bacterial mercury detoxification pathway. A member of the flavin disulfide oxidoreductase family, MerA contains an FAD prosthetic group and redox-active disulfide in its active site. However, the presence of these two moieties is not sufficient for catalytic Hg(II) reduction, as other enzyme family members are potently inhibited by mercurials. We have previously identified a second pair of active site cysteines (Cys558 Cys559 in the Tn501 enzyme) unique to MerA, that are essential for high levels of mercuric ion reductase activity [Moore, M. J., & Walsh, C. T. (1989) Biochemistry 28, 1183; Miller, S. M., et al. (1989) Biochemistry 28, 1194]. In this paper, we have examined the individual roles of Cys558 and Cys559 by site-directed mutagenesis of each to alanine. Phenotypic analysis indicates that both merA mutations result in a total disruption of the Hg(II) detoxification pathway in vivo, while characterization of the purified mutant enzymes in vitro shows each to have differential effects on catalytic function. Compared to wild-type enzyme, the C558A mutant shows a 20-fold reduction in kcat and a 10-fold increase in Km, for an overall decrease in catalytic efficiency of 200-fold in kcat/Km. In contrast, mutation of Cys559 to alanine results in less than a 2-fold reduction in kcat and an increase in Km of only 4-5 fold for an overall decrease in catalytic efficiency of only ca. 10-fold in vitro. From these results, it appears that Cys558 plays a more important role in forming the reducible complex with Hg(II), while both Cys558 and Cys559 seem to be involved in efficient scavenging (i.e., tight binding) of Hg(II).
Alanine↗
Policy options: early intervention services for substance-exposed infants.
Substance-exposed infants, or babies that have been victims of their mothers' drug use during pregnancy, have reached substantial proportions. Currently, no comprehensive public policy exists to deal with these infants as they enter a society unprepared to respond to an issue increasingly fraught with substantial adverse economic, social, and political ramifications. In order to address the needs of this emerging sub-population, California's governor and state legislature must develop and adopt a concerted interagency policy which outlines: a) uniform criteria for local health care workers, social service agencies, and educators; b) consistent guidelines governing the exchange of information among a range of agencies, including hospitals, schools, and other public and private agencies; and c) increased prevention and early intervention services for these babies and their families. Addressing the needs of these infants requires a bold, comprehensive, interdisciplinary approach from the creators of public policy.
California↗
Communication between the active sites in dimeric mercuric ion reductase: an alternating sites hypothesis for catalysis.
Mercuric reductase, a flavoprotein disulfide oxidoreductase, catalyzes the two-electron reduction of Hg(II) to Hg(0) by NADPH. As with all the members of this class of proteins, the enzyme is a dimer of identical subunits with two active sites per dimer, each composed of one FAD and catalytically essential residues from both subunits. In the enzyme from Tn501, these residues include, at a minimum, FAD and cysteines 135 and 140 from one subunit and cysteines 558' and 559' from the other. With this sort of active site arrangement, the enzyme seems perfectly set up for some type of subunit communication. In this report, we present results from several titrations, as well as kinetics studies, that, taken together, are consistent with the occurrence of subunit communication. In particular, the results indicate that pyridine nucleotide complexed dimers of the enzyme are asymmetric. Since the EH2-NADPH complex of the enzyme is the relevant reductant of Hg(II), these observations suggest that the enzyme may function asymmetrically during catalysis. An alternating sites model is proposed for the catalytic reduction of Hg(II), where both subunits of the dimer function in catalysis, but the steps are staggered and the subunits reverse roles after part of the reaction. An attractive feature of this proposal is that it provides a reasonable solution to the thermodynamic dilemma the enzyme faces in needing to both bind Hg(II) very tightly and reduce it.
Binding Sites↗
HIV infection after needlesticks.
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Accidents, Occupational↗
Adverse psychologic consequences of positive cytologic cervical screening.
Cervical cancer is still widely prevalent in the female population. This study explores the relationship of cervical cancer screening, positive versus negative Papanicolaou's test results, and psychologic status among lower-income minority women. All patients were interviewed 3 months after they had received initial test results. One hundred six women with normal Papanicolaou's test results were compared with 118 women who were referred for colposcopic examination for follow-up of positive test results. Women with positive Papanicolaou's-test results showed statistically significant elevations in worries about cancer and impairments in mood, daily activities, sexual interest, and sleep patterns. More fine-grained analyses revealed that the effects of positive results were most pronounced among those women who did not comply with colposcopy (n = 53). These findings suggest that lack of compliance with follow-up may maintain high levels of uncertainty about disease and may interfere with successful psychologic adaptation. Health education targeted to psychologically vulnerable individuals may reduce psychologic distress and enhance compliance.
Adolescent↗
Role of the complex upstream region of the GDH2 gene in nitrogen regulation of the NAD-linked glutamate dehydrogenase in Saccharomyces cerevisiae.
We analyzed the upstream region of the GDH2 gene, which encodes the NAD-linked glutamate dehydrogenase in Saccharomyces cerevisiae, for elements important for the regulation of the gene by the nitrogen source. The levels of this enzyme are high in cells grown with glutamate as the sole source of nitrogen and low in cells grown with glutamine or ammonium. We found that this regulation occurs at the level of transcription and that a total of six sites are required to cause a CYC1-lacZ fusion to the GDH2 gene to be regulated in the same manner as the NAD-linked glutamate dehydrogenase. Two sites behaved as upstream activation sites (UASs). The remaining four sites were found to block the effects of the two UASs in such a way that the GDH2-CYC1-lacZ fusion was not expressed unless the cells containing it were grown under conditions favorable for the activity of both UASs. This complex regulatory system appears to account for the fact that GDH2 expression is exquisitely sensitive to glutamine, whereas the expression of GLN1, coding for glutamine synthetase, is not nearly as sensitive.
Amino Acid Sequence↗
Physiological and genetic analysis of the carbon regulation of the NAD-dependent glutamate dehydrogenase of Saccharomyces cerevisiae.
We found that cells of Saccharomyces cerevisiae have an elevated level of the NAD-dependent glutamate dehydrogenase (NAD-GDH; encoded by the GDH2 gene) when grown with a nonfermentable carbon source or with limiting amounts of glucose, even in the presence of the repressing nitrogen source glutamine. This regulation was found to be transcriptional, and an upstream activation site (GDH2 UASc) sufficient for activation of transcription during respiratory growth conditions was identified. This UAS was found to be separable from a neighboring element which is necessary for the nitrogen source regulation of the gene, and strains deficient for the GLN3 gene product, required for expression of NAD-GDH during growth with the activating nitrogen source glutamate, were unaffected for the expression of NAD-GDH during growth with activating carbon sources. Two classes of mutations which prevented the normal activation of NAD-GDH in response to growth with nonfermentable carbon sources, but which did not affect the nitrogen-regulated expression of NAD-GDH, were found and characterized. Carbon regulation of GDH2 was found to be normal in hxk2, hap3, and hap4 strains and to be only slightly altered in a ssn6 strain; thus, in comparison with the regulation of previously identified glucose-repressed genes, a new pathway appears to be involved in the regulation of GDH2.
Blotting, Northern↗
Use of a site-directed triple mutant to trap intermediates: demonstration that the flavin C(4a)-thiol adduct and reduced flavin are kinetically competent intermediates in mercuric ion reductase.
A mutant form of mercuric reductase, which has three of its four catalytically essential cysteine residues replaced by alanines (ACAA: Ala135Cys140Ala558Ala559), has been constructed and used for mechanistic investigations. With disruption of the Hg(II) binding site, the mutant enzyme is devoid of Hg(II) reductase activity. However, it appears to fold properly since it binds FAD normally and exhibits very tight binding of pyridine nucleotides as is seen with the wild-type enzyme. This mutant enzyme allows quantitative accumulation of two species thought to function as intermediates in the catalytic sequence of the flavoprotein disulfide reductase family of enzymes. NADPH reduces the flavin in this mutant, and a stabilized E-FADH- form accumulates. The second intermediate is a flavin C(4a)-Cys140 thiol adduct, which is quantitatively accumulated by reaction of oxidized ACAA enzyme with NADP+. The conversion of the Cys135-Cys140 disulfide in wild-type enzyme to the monothiol Cys140 in ACAA and the elevated pKa of Cys140 (6.7 vs 5.0 in wild type) have permitted detection of these intermediates at low pH (5.0). The rates of formation of E-FADH- and the breakdown of the flavin C(4a)-thiol adduct have been measured and indicate that both intermediates are kinetically competent for both the reductive half-reaction and turnover by wild-type enzyme. These results validate the general proposal that electrons flow from NADPH to FADH- to C(4a)-thiol adduct to the FAD/dithiol form that accumulates as the EH2 form in the reductive half-reaction for this class of enzymes.
Amino Acid Sequence↗
Cloning and characterization of the 2,3-oxidosqualene cyclase-coding gene of Candida albicans.
2,3-Oxidosqualene (OS) cyclase (OSC) catalyzes the conversion of OS to lanosterol, an essential step in the biosynthesis of sterols. The Candida albicans gene (ERG7) encoding OSC was cloned by complementation of a Saccharomyces cerevisiae OSC mutant (erg7). Two different Erg+ clones were isolated that contain a common overlapping region. The minimum region required for complementation was determined to be approx. 3.2 kb and a single 2.7-kb ERG7 transcript was detected. The cloned Candida ERG7 DNA complemented an additional nonconditional erg7 allele and a temperature-sensitive erg7 mutation. OSC activity was restored in the mutants as determined by [14C]acetate incorporation in vivo as well as incorporation in vitro in cell-free extracts using either [14C]isopentenyl pyrophosphate or [3H]OS as substrate. The level of OSC produced from expression of a single copy of the Candida ERG7 sequence was sufficient to allow growth of the S. cerevisiae erg7 mutants in the absence of exogenous ergosterol. These data support the contention that the Candida ERG7 sequence is the structural gene for OSC.
Alleles↗