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Biomedical subjects

M Eisenberg

Publications and source records attributed to M Eisenberg.

At least 19 recordsLinked to original sources
PubMed1995

PCR analysis of HIV-seronegative, heterosexual partners of HIV-infected individuals.

A cohort of human immunodeficiency virus (HIV)-discordant couples was established to evaluate risk factors associated with heterosexual viral transmission. Polymerase chain reaction (PCR) was utilized to document the HIV-uninfected status among members of discordant heterosexual couples and to rule out immunosilent infection. HIV DNA PCR specific for a gag gene region was performed on peripheral blood mononuclear cell samples from 203 HIV antibody-negative adults who have long-term heterosexual relationships with HIV-infected partners. The results were negative for 200 but consistently positive in three individuals. More extensive evaluation of these three individuals with an additional primer pair specific for the envelope gene, quantitative DNA PCR, multiple additional time points, and variable nucleotide tandem repeat analyses revealed specimen processing problems in two cases but an apparent true positive PCR assay in the third case. This subject remains antibody and PCR negative for a 32-month follow-up period. These results confirm previous studies that document a negligible incidence of occult HIV infection as delineated by PCR in antibody negative heterosexual partners of HIV-infected individuals. Specimen processing errors occur at a low rate (1% in this study) and require careful evaluation. The possibility of transient, aborted infection versus successful infection with a long immunosilent period was observed in a single individual. Definitive resolution of infection status will require long-term evaluation.

Adult↗
PubMed1995

Causes of delay in seeking treatment for heart attack symptoms.

With the advent of thrombolytic therapy and other coronary reperfusion strategies, rapid identification and treatment of acute myocardial infarction greatly reduces mortality. Unfortunately, many patients delay seeking medical care and miss the benefits afforded by recent advances in treatment. Studies have shown that the median time from onset of symptoms to seeking care ranges from 2 to 61/2 hours, while optimal benefit is derived during the first hour from symptom onset. The phenomenon of delay by AMI patients and those around them needs to be understood prior to the design of education and counseling strategies to reduce delay. In this article the literature is reviewed and variables that increase patient delay are identified. A theoretical model based on the health belief model, a self regulation model of illness cognition, and interactionist role theory is proposed to explain the response of an individual to the signs and symptoms of acute myocardial infarction. Finally, recommendations are made for future research.

Attitude to Health↗
PubMed1995

Calculations of the electrostatic potential adjacent to model phospholipid bilayers.

We used the nonlinear Poisson-Boltzmann equation to calculate electrostatic potentials in the aqueous phase adjacent to model phospholipid bilayers containing mixtures of zwitterionic lipids (phosphatidylcholine) and acidic lipids (phosphatidylserine or phosphatidylglycerol). The aqueous phase (relative permittivity, epsilon r = 80) contains 0.1 M monovalent salt. When the bilayers contain < 11% acidic lipid, the -25 mV equipotential surfaces are discrete domes centered over the negatively charged lipids and are approximately twice the value calculated using Debye-Hückel theory. When the bilayers contain > 25% acidic lipid, the -25 mV equipotential profiles are essentially flat and agree well with the values calculated using Gouy-Chapman theory. When the bilayers contain 100% acidic lipid, all of the equipotential surfaces are flat and agree with Gouy-Chapman predictions (including the -100 mV surface, which is located only 1 A from the outermost atoms). Even our model bilayers are not simple systems: the charge on each lipid is distributed over several atoms, these partial charges are non-coplanar, there is a 2 A ion-exclusion region (epsilon r = 80) adjacent to the polar headgroups, and the molecular surface is rough. We investigated the effect of these four factors using smooth (or bumpy) epsilon r = 2 slabs with embedded point charges: these factors had only minor effects on the potential in the aqueous phase.

Biophysical Phenomena↗
PubMed1995

CPR instruction by videotape: results of a community project.

STUDY OBJECTIVE: To increase the rate of bystander CPR in a community by use of a free, mailed, 10-minute videotape of CPR instruction. DESIGN: Prospective, randomized intervention trial. One half of the households (8,659) received the free videotape (video-tape group) and were considered the intervention group, and one half (8,659) served as the control (no-videotape group). All households were followed from December 1991 to March 1993 to determine whether a cardiac arrest occurred and who initiated CPR. A telephone interview obtained additional information about circumstances of the arrest and whether members of the household viewed the videotape. SETTING: City of Everett and South Snohomish County, Washington. A commercial mailing list was used to identify 17,318 households with a head of the household who was more than 50 years old. PARTICIPANTS: A case was defined as a cardiac arrest in which CPR was initiated or continued by emergency medical services personnel. Only cardiac arrests due to presumed underlying heart disease were included. Arrests occurring after arrival of emergency medical services personnel were not included. INTERVENTIONS: The intervention was a free 10-minute videotape with CPR instructions mailed to the 8,659 intervention households. Paramedic run reports were reviewed and interviews were conducted with cardiac arrest bystanders to determine who initiated CPR and whether they had received and viewed the videotape. RESULTS: Sixty-five cardiac arrests occurred in the study households: 31 in households that received the videotape and 34 in households that did not review the videotape. The overall rate of bystander CPR was 47% in the videotape group and 53% in the no-videotape group (P = NS). In nine cardiac arrests, an individual was present who had watched the videotape; six of these nine cases (66%) had bystander CPR. CONCLUSION: Mass mailings of CPR instructional videos are likely to be ineffective in increasing the rate of bystander CPR in a community.

Aged↗
PubMed1995

Management of the vertebral artery in excision of extradural tumors of the cervical spine.

Extradural tumors of the cervical spine may involve the vertebral artery on one or both sides, posing one of the limiting factors toward the radical resection of such neoplasms. A standard anterior approach may be inadequate for the management of such tumors. An anterolateral approach allows the dissection and mobilization of the vessel, which can then be preserved, resected, or reconstructed with a vein graft. An anterior approach can be supplemented with this for tumor resection and stabilization. This management strategy is described in 10 patients with a variety of tumors.

Adolescent↗
PubMed1994

Accuracy of determining cardiac arrest by emergency medical dispatchers.

STUDY OBJECTIVE: To identify and determine the rates of delivery and performance of telephone CPR in noncardiac arrest incidents. DESIGN: We studied prospectively all out-of-hospital cardiac arrest and potential cardiac arrest incidents from July 1 through October 31, 1992. SETTING: King County, Washington, excluding the city of Seattle. PARTICIPANTS: Persons with cardiac arrest or an initial complaint resembling cardiac arrest who received emergency medical services. INTERVENTIONS: Dispatcher-assisted telephone CPR. MEASUREMENTS AND MAIN RESULTS: Three hundred fifty-eight incidents of cardiac arrest, respiratory arrest, and potential cardiac arrest were reviewed. Telephone CPR was offered appropriately in 61 of 87 cases (70%) and inappropriately in eight of 154 potential cardiac arrests (5.2%) (95% confidence interval, 1.7%, 8.7%). Ventilation instructions were performed appropriately in 52 of 87 cases (60%) and inappropriately in three of 154 potential cardiac arrests (1.9%) (95% confidence interval, 0%, 4.1%). Chest compressions were performed appropriately in 26 of 68 cardiac arrests (38.2%) and inappropriately in two of 173 potential cardiac arrests (1.2%) (95% confidence interval, 0%, 2.8%). CONCLUSION: We found a low rate of performance of telephone CPR in King County for incidents resembling cardiac arrest. This finding suggests that the protocols designed for dispatcher-assisted telephone CPR effectively screen out those incidents that may initially resemble cardiac arrest.

Adult↗
PubMed1993

Prehospital-initiated vs hospital-initiated thrombolytic therapy. The Myocardial Infarction Triage and Intervention Trial.

OBJECTIVE: To determine the effect of prehospital-initiated vs hospital-initiated treatment of myocardial infarction on clinical outcome. DESIGN: Randomized, controlled clinical trial. SETTING: Multicenter study involving 19 hospitals and all paramedic systems in the Seattle, Wash, metropolitan area. PATIENTS: A total of 360 patients with symptoms for 6 hours or less, no risk factors for serious bleeding, and ST-segment elevation were selected by paramedics and a remote physician for inclusion into the trial. They represented 4% of patients with chest pain who were screened and 21% of those with acute infarction. INTERVENTIONS: Patients were allocated to have aspirin and alteplase treatment initiated before or after hospital arrival. Intravenous sodium heparin was administered to both groups in the hospital. MAIN OUTCOME MEASURE: The primary endpoint was a ranked composite score (combining death, stroke, serious bleeding, and infarct size). The relation between time to treatment and outcome (composite score, infarct size, ejection fraction, and mortality) was also assessed. RESULTS: Initiating treatment before hospital arrival decreased the interval from symptom onset to treatment from 110 to 77 minutes (P < .001). Although more patients whose therapy was initiated before hospital arrival had resolution of pain by admission (23% vs 7%; P < .001), there were no significant differences in the composite score (P = .64), mortality (5.7% vs 8.1%), ejection fraction (53% vs 54%), or infarct size (6.1% vs 6.5%). A secondary analysis of time to treatment and outcome showed that treatment initiated within 70 minutes of symptom onset was associated with better outcome (composite score, P = .009; mortality, 1.2% vs 8.7%, P = .04; infarct size, 4.9% vs 11.2%, P < .001; and ejection fraction, 53% vs 49%, P = .03) than later treatment. Identification of patients eligible for thrombolysis by paramedics reduced the hospital treatment time from 60 minutes (for patients not in the study) to 20 minutes (for study patients allocated to begin treatment in the hospital). CONCLUSION: There was no improvement in outcome associated with initiating treatment before hospital arrival; however, treatment within 70 minutes of symptom onset--whether in the hospital or in the field--minimized the infarct process and its complications.

Aged↗
PubMed1993

Solution structure of the exocyclic 1,N2-propanodeoxyguanosine adduct opposite deoxyadenosine in a DNA nonamer duplex at pH 8.9. model of pH-dependent conformational transition.

The solution structure of the complementary d(C1-A2-T3-G4-X5-G6-T7-A8-C9).d(G10-T11-A12-C13-A14-C15-A16-T17-G18) DNA duplex (designated X.A 9-mer), which contains a 1,N2-propanodeoxyguanosine exocyclic adduct X5 opposite deoxyadenosine A14 at the center, is pH dependent [Kouchakdjian, M., Eisenberg, M., Live, D., Marinelli, E., Grollman, A., & Patel, D.J. (1990) Biochemistry 29, 4456-4465]. In our previous paper [Huang, P., & Eisenberg, M. (1992) Biochemistry 31, 6518-6532] we established the three-dimensional structure of this X.A 9-mer duplex at pH 5.8 by use of restrained molecular dynamics followed by NOE-based back-calculation refinement. The present paper discusses the structure at pH 8.9 and the pH-dependent conformational transition between the structures at pH 5.8 and at pH 8.9. The structure at pH 8.9 is calculated starting from five different conformations. The final structures converge and agree well with the experimental NOE intensities. These structures are essentially B-type DNA (with X5 and A14 in the BII conformation while the other residues are in the most commonly described BI conformation) and display an approximate 27 degrees kink at the center of the helix. At the kink site, X5 is positioned in the major groove with the exocyclic ring directed toward the G6.C13 base pair, unstacked from the flanking base G6 and exposed to the solvent. A14, opposite the lesion, remains stacked with its neighbor C15, but not with C13. The kinked helix can accommodate the rotation of the bulky X5 about its glycosidic bond. We propose here a model for the pH-dependent transition. Our model explains the conformational change, which includes the anti and syn rotation of the bulky adduct around its glycosidic bond, with a minimal energy barrier and with an overall kink of the DNA helix. These new findings, fully consistent with the NMR experimental data, were revealed only after restrained dynamics refinement. Distance-restrained energy minimization by itself was insufficient, as shown by the previous NMR study.

Base Sequence↗
PubMed1993

Structure of the rudimentary-like gene and UMP synthase in Drosophila melanogaster.

The last two steps of de novo UMP biosynthesis are performed by a bi-enzymic protein in animal cells, UMP synthase, that is encoded by the gene r-l in Drosophila melanogaster. Over 3.5 kb of genomic DNA spanning this gene were sequenced. Transcriptional organization of r-l has been determined by sequence analysis of two cDNA clones and by primer extension analysis of embryonic RNA. The DNA region 5' to the apparent transcription start point contains no known transcriptional control elements or sequences similar to those upstream from dhod, which encodes the metabolic pathway step preceding UMP synthase. The deduced protein of 53.5 kDa is similar to the UMP synthases of slime molds and humans. It contains the two enzymatic domains separated by an apparent bridge polypeptide sequence of over 30 amino acids, which is dissimilar among UMP synthases of different organisms. The r-l structure includes two introns, one of which occurs within the DNA region that encodes the interdomain bridge sequence of the protein.

Amino Acid Sequence↗
PubMed1992

The three-dimensional structure in solution (pH 5.8) of a DNA 9-mer duplex containing 1,N2-propanodeoxyguanosine opposite deoxyadenosine. Restrained molecular dynamics and NOE-based refinement calculations.

The solution structure of the complementary d(C1-A2-T3-G4-X5-G6-T7-A8-C9).d(G10-T11-A12-C13-A14-C15-A 16-T17-G18) nonanucleotide duplex (designated X.A 9-mer) that contains a 1,N2-propanodeoxyguanosine exocyclic adduct, X5, opposite deoxyadenosine A14 in the center of the helix at pH 5.8 is investigated by use of restrained molecular dynamics followed by NOE-based back-calculation refinement. The molecular dynamics calculation is based on 91 interresidue and 97 intraresidue interproton distance restraints derived from two-dimensional nuclear Overhauser enhancement data on the X.A 9-mer at mixing times of 50 and 250 ms [Kouchakdjian, M., Marinelli, E., Gao, X., Johnson, F., Grollman, A., & Patel, D.J. (1989) Biochemistry 28, 5647-5657]. Separate runs start from classical A and B DNA and converge to essentially identical structures (atomic root mean square difference of 0.69 A). Both structures are B-type DNA in character and satisfy the experimental distance restraints with the rms difference of only 0.001 A between the calculated and experimental interproton distances. The dynamics behavior of the A----B DNA transition is monitored and analyzed. Our results clearly indicate that the driving force of the convergence is the experimental interproton distance restraints. The molecular dynamics structures are further refined by a back-calculation dynamics which directly minimizes the difference between the observed 2D NOE intensities and those calculated by the full relaxation matrix approach. The fit of the refined structures to the NOE intensities is measured by the NOE R value, which is analogous to the crystallographic residual index. These R values of the final structures are only 0.17. The refined structures are generally B type, and their convergency improves slightly to an atomic root mean square difference of 0.64 A, despite relatively large structural shifts (approximately 1 A) which occur during the back-calculation refinement in both cases. These results suggest that the converged refined structures represent reasonable approximations of the solution structure.

Base Sequence↗
PubMed1991

Structural features of an exocyclic adduct positioned opposite an abasic site in a DNA duplex.

Structural studies have been extended to dual lesions where an exocyclic adduct is positioned opposite an abasic site in the center of a DNA oligomer duplex. NMR and energy minimization studies were performed on the 1,N2-propanodeoxyguanosine exocyclic adduct (X) positioned opposite a tetrahydrofuran abasic site (F) with the dual lesions located in the center of the (C1-A2-T3-G4-X5-G6-T7-A8-C9).(G10-T11-A12-C-13-F14-C15 -A16-T17-G-18) X.F 9-mer duplex. Two-dimensional NMR experiments establish that the X.F 9-mer helix is right-handed with Watson-Crick A.T and G.C base pairing on either side of the lesion site. NOEs are detected from the methylene protons of the exocyclic ring of X5 to the imino protons of G4.C15 and G6.C13 which flank the lesion site, as well as to the H1' and H1" protons of the cross strand F14 tetrahydrofuran moiety. These NMR results establish that the exocyclic adduct X5 is positioned between flanking G4.C15 and G6.C13 base pairs and directed toward the abasic lesion F14 on the partner strand. These studies establish that the exocyclic ring of the 1,N2-propanodeoxyguanosine adduct fits into the cavity generated by the abasic site.

Base Composition↗
PubMed1991

NMR studies of the exocyclic 1,N6-ethenodeoxyadenosine adduct (epsilon dA) opposite thymidine in a DNA duplex. Nonplanar alignment of epsilon dA(anti) and dT(anti) at the lesion site.

Two-dimensional proton NMR studies are reported on the complementary d(C-A-T-G-T-G-T-A-C).d(G-T-A-C-epsilon A-C-A-T-G) nonanucleotide duplex (designated epsilon dA.dT 9-mer duplex) containing 1,N6-ethenodeoxyadenosine (epsilon dA), a carcinogen-DNA adduct, positioned opposite thymidine in the center of the helix. Our NMR studies have focused on the conformation of the epsilon dA.dT 9-mer duplex at neutral pH with emphasis on defining the alignment at the dT5.epsilon dA14 lesion site. The through-space NOE distance connectivities establish that both dT5 and epsilon dA14 adopt anti glycosidic torsion angles, are directed into the interior of the helix, and stack with flanking Watson-Crick dG4.dC15 and dG6.dC13 pairs. Furthermore, the d(G4-T5-G6).d(C13-epsilon A14-C15) trinucleotide segment centered about the dT5.epsilon dA14 lesion site adopts a right-handed helical conformation in solution. Energy minimization computations were undertaken starting from six different alignments of dT5(anti) and epsilon dA14(anti) at the lesion site and were guided by distance constraints defined by lower and upper bounds estimated from NOESY data sets on the epsilon dA.dT 9-mer duplex. Two families of energy-minimized structures were identified with the dT5 displaced toward either the flanking dG4.dC15 or the dG6.dC13 base pair. These structures can be differentiated on the basis of the observed NOEs from the imino proton of dT5 to the imino proton of dG4 but not dG6 and to the amino protons of dC15 but not dC13 that were not included in the constraints data set used in energy minimization. Our NMR data are consistent with a nonplanar alignment of epsilon dA14(anti) and dT5(anti) with dT5 displaced toward the flanking dG4.dC15 base pair within the d(G4-T5-G6).d(C13-epsilon A14-C15) segment of the epsilon dA.dT 9-mer duplex.

Adenosine↗
PubMed1991

NMR structural studies of the ionizing radiation adduct 7-hydro-8-oxodeoxyguanosine (8-oxo-7H-dG) opposite deoxyadenosine in a DNA duplex. 8-Oxo-7H-dG(syn).dA(anti) alignment at lesion site.

Proton NMR studies are reported on the complementary d(C1-C2-A3-C4-T5-A6-oxo-G7-T8-C9-A10-C11-C12).d(G13-G14-T15- G16-A17-A18-T19- A20-G21-T22-G23-G24) dodecanucleotide duplex (designated 8-oxo-7H-dG.dA 12-mer), which contains a centrally located 7-hydro-8-oxodeoxyguanosine (8-oxo-7H-dG) residue, a group commonly found in DNA that has been exposed to ionizing radiation or oxidizing free radicals. From the NMR spectra it can be deduced that this moiety exists as two tautomers, or gives rise to two DNA conformations, that are in equilibrium and that exchange slowly. The present study focuses on the major component of the equilibrium that originates in the 6,8-dioxo tautomer of 8-oxo-7H-dG. We have assigned the exchangeable NH1, NH7, and NH2-2 base protons located on the Watson-Crick and Hoogsteen edges of 8-oxo-7H-dG7 in the 8-oxo-7H-dG.dA 12-mer duplex, using an analysis of one- and two-dimensional nuclear Overhauser enhancement (NOE) data in H2O solution. The observed NOEs derived from the NH7 proton of 8-oxo-7H-dG7 to the H2 and NH2-6 protons of dA18 establish an 8-oxo-7H-dG7(syn).dA 18(anti) alignment at the lesion site in the 8-oxo-7H-dG.dA 12-mer duplex in solution. This alignment, which places the 8-oxo group in the minor groove, was further characterized by an analysis of the NOESY spectrum of the 8-oxo-7H-dG.dA 12-mer duplex in D2O solution. We were able to detect a set of intra- and interstrand NOEs between protons (exchangeable and nonexchangeable) on adjacent residues in the d(A6-oxo-G7-T8).d(A17-A18-T19) trinucleotide segment centered about the lesion site that establishes stacking of the oxo-dG7(syn).dA(anti) pair between stable Watson-Crick dA6.dT19 and dT8.dA17 base pairs with minimal perturbation of the helix. Thus, both strands of the 8-oxo-7H-dG.dA 12-mer duplex adopt right-handed conformations at and adjacent to the lesion site, the unmodified bases adopt anti glycosidic torsion angles, and the bases are stacked into the helix. The energy-minimized conformation of the central d(A6-oxo-G7-T8).d(A17-A18-T19) segment requires that the 8-oxo-7H-dG7(syn).dA18(anti) alignment be stabilized by two hydrogen bonds from NH7 and O6 of 8-oxo-7H-dG7(syn) to N1 and NH2-6 of dA18(anti), respectively, at the lesion site.(ABSTRACT TRUNCATED AT 400 WORDS)

8-Hydroxy-2'-Deoxyguanosine↗