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Biomedical subjects

R Davis

Publications and source records attributed to R Davis.

At least 217 records · Page 12Linked to original sources
PubMed1995

Impact of sexual and nonsexual assault on secondary victims.

Much information has been collected on the effects of crime upon victims. Experts have spoken as well about the ripple effects of crime on those close to victims. To date, however, little empirical data are available to assess the impact of crime upon "secondary victims." Our research looks at the effects of crime on a sample of persons named by victims of sexual and nonsexual assault as their primary significant others (SOs). We found that distress experienced by SOs did not vary according to victim distress or according to whether the crime was a sexual or nonsexual assault. Female SOs, however, experienced greater fear of crime than male SOs. High levels of SO distress did not interfere with the ability of SOs to lend supportive actions, but were associated with higher levels of SO unsupportive behavior. Higher levels of unsupportive behavior were also more likely among SOs of sexual assault victims than among SOs of nonsexual assault victims. Clinical implications of the findings are discussed.

Adaptation, Psychological↗
PubMed1994

JNK2 contains a specificity-determining region responsible for efficient c-Jun binding and phosphorylation.

The transcriptional activity of c-Jun is augmented through phosphorylation at two sites by a c-Jun amino-terminal kinase (JNK). All cells express two distinct JNK activities, 46 and 55 kD in size. It is not clear which of them is the more important c-Jun kinase and how they specifically recognize c-Jun. The 46-kD form of JNK was identified as a new member of the MAP kinase group of signal-transducing enzymes, JNK1. Here, we report the molecular cloning of the 55-kD form of JNK, JNK2, which exhibits 83% identity and similar regulation to JNK1. Despite this close similarity, the two JNKs differ greatly in their ability to interact with c-Jun. JNK2 binds c-Jun approximately 25 times more efficiently than JNK1, and as a result has a lower Km toward c-Jun than JNK1. The structural basis for this difference was investigated and traced to a small beta-strand-like region near the catalytic pocket of the enzyme. Modeling suggests that this region is solvent exposed and therefore is likely to serve as a docking site that increases the effective concentration of c-Jun near JNK2. These results explain how two closely related MAP kinases can differ in their ability to recognize specific substrates and thereby elicit different biological responses.

Amino Acid Sequence↗
PubMed1994

Purification, characterization, and localization of subunit interaction area of recombinant mouse ribonucleotide reductase R1 subunit.

Mammalian ribonucleotide reductase is a heterotetramer formed by the two non-identical homodimers proteins R1 and R2. We have succeeded in expressing the 90-kDa mouse R1 protein in Escherichia coli in an active, soluble form using the T7 RNA polymerase pET vector system. To avoid inclusion bodies, the bacteria were grown at 15 degrees C with minimal concentration of the inducer isopropyl-1-thio-beta-D-galactopyranoside. After a rapid purification procedure, approximately 20 mg of pure R1 protein were obtained per liter of bacterial culture. The concentrated R1 protein solution had a pinkish red color. Spectroscopy in combination with iron and labile sulfur analyses demonstrated that the color originated from an iron-sulfur complex. However, all attempts to demonstrate a function of this complex have been inconclusive. A comparison of the recombinant R1 protein with the corresponding protein purified from calf thymus showed no evidence for glycosylation. Circular dichroism spectroscopy indicated an alpha-helical content of 50%. A flexible COOH-terminal tail of 7 residues in the R2 protein was earlier shown to be essential for binding to the R1 protein. Using a peptide protection assay and photoaffinity labeling, we now show that the R2 protein tail interacts with a region close to the carboxyl terminus of the R1 protein.

Affinity Labels↗
PubMed1994

1H NMR studies of mouse ribonucleotide reductase: the R2 protein carboxyl-terminal tail, essential for subunit interaction, is highly flexible but becomes rigid in the presence of protein R1.

Mouse ribonucleotide reductase consists of two nonidentical subunits, proteins R1 and R2, each inactive alone. It has earlier been shown that the carboxyl-terminal part of the R2 protein is essential for subunit association to form the active enzyme complex. We now demonstrate that protein R2 gives rise to a number of sharp 1H NMR resonances, significantly narrower than the major part of the resonances. This line narrowing of certain resonances indicates segmental mobility in the molecule. In two-dimensional 1H TOCSY spectra of protein R2, cross-peak patterns from about 25 amino acid residues are visible. Most of these were assigned to the carboxyl-terminal part of the protein by comparisons with cross-peak patterns of oligopeptides corresponding to the carboxyl terminus of mouse R2 and to the patterns of a seven amino acid residue carboxyl-terminal truncated form of protein R2. These results and the magnitude of the chemical shifts of the assigned residues demonstrate that the carboxyl-terminal part of mouse R2 protein is highly mobile compared to the rest of the protein and essentially unstructured. When protein R1 is added to a solution of protein R2, the sharp resonances are broadened, suggesting that the mobility of the carboxyl-terminal tail of protein R2 is reduced. The possibility of making direct observations of subunit interaction in native and mutagenized R1/R2 proteins should allow discrimination between effects of amino acid replacements on the catalytic mechanism and effects on subunit interaction.

Amino Acid Sequence↗
PubMed1994

DNA sequence confidence estimation.

A significant bottleneck in the current DNA sequencing process is the manual editing of trace data generated by automated DNA sequencers. This step is used to correct base calls and to associate to each base call a confidence level. The confidence levels are used in the assembly process to determine overlaps and to resolve discrepancies in determining the consensus sequence. This single step may cost as much as 4 to 8 cents per finished base. We report an approach to automated trace editing using classification trees to detect and exploit context-based patterns in trace peak heights. Local base composition and nearby peak heights account for 80% of the variations in peak heights. Classification algorithms were developed to identify 37% of automated base calls that differ from the consensus sequence. With these algorithms, 12% of the base calls had confidence levels less than 90%.

Algorithms↗
PubMed1994

Trimetrexate with leucovorin versus trimethoprim-sulfamethoxazole for moderate to severe episodes of Pneumocystis carinii pneumonia in patients with AIDS: a prospective, controlled multicenter investigation of the AIDS Clinical Trials Group Protocol 029/031.

Trimetrexate is a powerful inhibitor of the dihydrofolate reductase of Pneumocystis carinii. AIDS patients (n = 215) with moderate to severe P. carinii pneumonia were enrolled in a double-blind study of trimetrexate plus leucovorin versus trimethoprim-sulfamethoxazole (TMP-SMZ) for 21 days. By study day 10, study therapy failed because of lack of efficacy in 16% of patients assigned to TMP-SMZ and 27% assigned to trimetrexate (P = .064), and the PAO2-PaO2 improved significantly faster with TMP-SMZ. By study day 21, failure rates were 20% with TMP-SMZ and 38% with trimetrexate (P = .008), with respective mortality rates of 12% and 20% (P = .088). By study day 49, the difference in mortality (16% vs. 31%) was significant (P = .028). The cumulative incidence of serious and treatment-terminating adverse events including hematologic toxicities was less with trimetrexate (P < .001). Thus, trimetrexate plus leucovorin was effective, albeit inferior to TMP-SMZ, for moderately severe P. carinii pneumonia but was better tolerated than TMP-SMZ.

AIDS-Related Opportunistic Infections↗
PubMed1994

Phase II dose-ranging trial of foscarnet salvage therapy for cytomegalovirus retinitis in AIDS patients intolerant of or resistant to ganciclovir (ACTG protocol 093). AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases.

OBJECTIVE: To document response to foscarnet salvage therapy in patients with cytomegalovirus (CMV) retinitis who are intolerant of or resistant to ganciclovir. METHODS: Patients with AIDS and CMV retinitis who had documented hematologic intolerance or resistance to ganciclovir therapy received an induction course of foscarnet, 60 mg/kg every 8 h for 14 days, and subsequent chronic maintenance foscarnet therapy at a daily dose of 60, 90 or 120 mg/kg/day. The first 87 patients were randomly assigned to receive maintenance foscarnet at a dose of 60 or 90 mg/kg/day; all subsequent patients were assigned a maintenance dose of 120 mg/kg/day. RESULTS: A total of 156 evaluable patients were enrolled. Median time to retinitis progression and survival did not differ significantly among groups assigned to different maintenance foscarnet doses. Among patients with retinitis progression documented ophthalmologically occurring at < or = 2 week intervals, despite optimal doses of ganciclovir, time to progression on foscarnet therapy was a median 8 weeks at all doses studied. By dose assignment, there were no significant differences in serious drug-associated toxicity, although trends toward increased renal and hypocalcemic adverse events were observed at higher maintenance doses. CONCLUSION: In patients intolerant of ganciclovir, salvage foscarnet therapy resulted in a longer time to retinitis progression than reported previously in historic controls who terminated ganciclovir therapy. In patients who exhibited clinical resistance to ganciclovir, foscarnet appeared to have efficacy in controlling retinitis. No significant differences in either efficacy or toxicity were observed in the range of foscarnet maintenance doses studied.

AIDS-Related Opportunistic Infections↗
PubMed1994

Pharmacodynamic relationship of pharmacokinetic parameters of maintenance doses of foscarnet and clinical outcome of cytomegalovirus retinitis.

The pharmacodynamic relationship between a range of foscarnet exposure measurements obtained from studying nine patients receiving ongoing maintenance therapy for cytomegalovirus retinitis and a range of efficacy values (days to retinitis progression) obtained by independent examination of serial retinal photographs from the same nine patients was analyzed. In the resulting proportional hazards models, the foscarnet area under the concentration-time curve approached statistical significance (P = 0.11) as a predictor of decreased risk of retinitis progression.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Serotypes of Streptococcus pneumoniae blood culture isolates from adults in Franklin County, Ohio.

Isolates of Streptococcus pneumoniae in cultures of blood from 258 adults seen in 10 Franklin County, Ohio, hospitals from 1991 and 1992 were serotyped. Most strains (230 [89.2%]) belonged to serotypes that are included in the current pneumococcal vaccine. An additional 16 isolates (6.2%) were immunologically related to strains with serotypes that are included in the vaccine. Only 12 isolates (4.6%) were not covered by the vaccine. The rate of mortality from pneumococcal bacteremia in adults remains high (20%). While recent studies have documented the efficacy of the pneumococcal vaccine for preventing pneumococcal bacteremia (56 to 70%), use of the pneumococcal vaccine in susceptible patients by physicians remains low (19% in Franklin County). Additional efforts need to be expended to increase the use of the pneumococcal vaccine.

Adult↗
PubMed1994

c-Jun N-terminal phosphorylation correlates with activation of the JNK subgroup but not the ERK subgroup of mitogen-activated protein kinases.

c-Jun transcriptional activity is stimulated by phosphorylation at two N-terminal sites: Ser-63 and -73. Phosphorylation of these sites is enhanced in response to a variety of extracellular stimuli, including growth factors, cytokines, and UV irradiation. New members of the mitogen-activated protein (MAP) kinase group of signal-transducing enzymes, termed JNKs, bind to the activation domain of c-Jun and specifically phosphorylate these sites. However, the N-terminal sites of c-Jun were also suggested to be phosphorylated by two other MAP kinases, ERK1 and ERK2. Despite these reports, we find that unlike the JNKs, ERK1 and ERK2 do not phosphorylate the N-terminal sites of c-Jun in vitro; instead they phosphorylate an inhibitory C-terminal site. Furthermore, the phosphorylation of c-Jun in vivo at the N-terminal sites correlates with activation of the JNKs but not the ERKs. The ERKs are probably involved in the induction of c-fos expression and thereby contribute to the stimulation of AP-1 activity. Our study suggests that two different branches of the MAP kinase group are involved in the stimulation of AP-1 activity through two different mechanisms.

Animals↗
PubMed1994

Initial results of the nucleus FES-22-implanted system for limb movement in paraplegia.

The Nucleus 'FES-22' channel stimulation system has been developed for partial restoration of lower limb function in paraplegic individuals. One FES-22 stimulator has been implanted in a 25-year-old paraplegic subject in November 1991. Of the twenty 2.5-mm disc electrodes attached epineurally onto motor nerves, fifteen are capable of producing observable threshold and maximal muscle contractions with joint movements.

Adult↗