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Biomedical subjects

B A Shapiro

Publications and source records attributed to B A Shapiro.

At least 19 recordsLinked to original sources
PubMed1992

Extensive sequence-specific information throughout the CAR/RRE, the target sequence of the human immunodeficiency virus type 1 Rev protein.

The significance and location of sequence-specific information in the CAR/RRE, the target sequence for the Rev protein of the human immunodeficiency virus type 1 (HIV-1), have been controversial. We present here a comprehensive experimental and computational approach combining mutational analysis, phylogenetic comparison, and thermodynamic structure calculations with a systematic strategy for distinguishing sequence-specific information from secondary structural information. A target sequence analog was designed to have a secondary structure identical to that of the wild type but a sequence that differs from that of the wild type at every position. This analog was inactive. By exchanging fragments between the wild-type sequence and the inactive analog, we were able to detect an unexpectedly extensive distribution of sequence specificity throughout the CAR/RRE. The analysis enabled us to identify a critically important sequence-specific region, region IIb in the Rev-binding domain, strongly supports a proposed base-pairing interaction in this location, and places forceful constraints on mechanisms of Rev action. The generalized approach presented can be applied to other systems.

Base Sequence↗
PubMed1992

Concurrent bacterial lung infection in patients with AIDS, PCP, and respiratory failure.

STUDY OBJECTIVES: To determine and compare the incidence of concurrent bacterial lung infection in intubated and nonintubated patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia (PCP) requiring medical intensive care unit (MICU) admission for support of their respiratory function. DESIGN: Retrospective review of medical records. SETTING: A large university hospital and AIDS treatment center. PATIENTS: All AIDS/PCP patients admitted to the MICU for support of oxygenation and/or ventilation between 1985 and 1989. Survival was defined as discharge from the hospital; nonsurvival was defined as death any time during the hospitalization. Patients with acute spinal cord injury (SCI) were used as controls to determine the incidence of nosocomial pneumonia in ICU patients of similar age without AIDS. MEASUREMENTS AND RESULTS: Twenty-nine AIDS/PCP patients met study criteria; eight (28 percent) were survivors and 21 (72 percent) were nonsurvivors. There was no significant difference in duration of intubation or duration of ICU stay between survivors and nonsurvivors with or without intubation. The incidence of bacterial concurrent lung infection (CLI) in AIDS/PCP patients overall was 7 percent and in intubated AIDS/PCP patients it was 10 percent. There was no statistically significant difference in the incidence of bacterial CLI between the survivors and nonsurvivors or between intubated and nonintubated patients with AIDS/PCP. The incidence of nosocomial pneumonia in SCI overall was 17 percent and in intubated SCI patients it was 30 percent. CONCLUSIONS: The incidence of bacterial lung infections in our retrospective study of AIDS patients with PCP is remarkably less than in the general ICU population with respiratory failure and in our control patients with SCI, although the differences did not attain statistical significance. This finding may be related to antimicrobial therapy directed against P carinii. Endotracheal intubation in patients with AIDS and PCP, who were undergoing appropriate antimicrobial therapy, did not result in a significantly higher incidence of bacterial lung infections than in those who were not intubated. There was no significant difference in the incidence of bacterial lung infections between those AIDS/PCP patients who survived episodes of severe respiratory failure and those who did not. Endotracheal intubation should not be delayed or withheld from this patient population due to concerns of pulmonary bacterial superinfection.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Functional importance of sequence in the stem-loop of a transcription terminator.

Intrinsic transcription terminators of prokaryotes are distinguished by a common RNA motif: a stem-loop structure high in guanine and cytosine content, followed by multiple uridine residues. Models explaining intrinsic terminators postulate that the stem-loop sequence is necessary only to form structure. In the tR2 terminator of coliphage lambda, single-nucleotide changes reducing potential RNA stem stability eliminated tR2 activity, and a compensatory change that restored the stem structure restored terminator activity. However, multiple changes in the stem sequence that should have either maintained or increased stability reduced terminator activity. These results suggest that the ability of the stem-loop structure to signal transcription termination depends on sequence specificity and secondary structure.

Bacteriophage lambda↗
PubMed1991

RNA pseudoknots downstream of the frameshift sites of retroviruses.

RNA pseudoknot structural motifs could have implications for a wide range of biological processes of RNAs. In this study, the potential RNA pseudoknots just downstream from the known and suspected retroviral frame-shift sites were predicted in the Rous sarcoma virus, primate immunodeficiency viruses (HIV-1, HIV-2, and SIV), equine infectious anemia virus, visna virus, bovine leukemia virus, human T-cell leukemia virus (types I and II), mouse mammary tumor virus, Mason-Pfizer monkey virus, and simian SRV-1 type-D retrovirus. Also, the putative RNA pseudoknots were detected in the gag-pol overlaps of two retrotransposons of Drosophila, 17.6 and gypsy, and the mouse intracisternal A particle. For each sequence, the thermodynamic stability and statistical significance of the secondary structure involved in the predicted tertiary structure were assessed and compared. Our results show that the stem-loop structures in the pseudoknots are both thermodynamically highly stable and statistically significant relative to other such configurations that potentially occur in the gag-pol or gag-pro and pro-pol junction domains of these viruses (300 nucleotides upstream and downstream from the possible frameshift sites are included). Moreover, the structural features of the predicted pseudoknots following the frameshift site of pro-pol overlaps of the HTLV-1 and HTLV-2 retroviruses are structurally well conserved. The occurrence of eight compensatory base changes in the tertiary interaction of the two related sequences allow the conservation of their tertiary structures in spite of the sequence divergence. The results support the possible control mechanism for frameshifting proposed by Brierley et al. and Jacks et al.

Base Sequence↗
PubMed1991

Intensive care unit patients with acquired immunodeficiency syndrome and Pneumocystis carinii pneumonia: suggested predictors of hospital outcome.

OBJECTIVE: To define our ICU experience with AIDS patients, Pneumocystis carinii pneumonia, and respiratory failure, and to delineate factors predictive of hospital survival. DESIGN: A retrospective study in which logistic regression analysis was applied to data obtained during the first 144 hrs of ICU admission. SETTING: A university hospital medical ICU associated with a national AIDS treatment center. PATIENTS: Twenty-seven male patients with AIDS, P. carinii pneumonia, and respiratory failure who desired full supportive and resuscitative care. MEASUREMENTS AND MAIN RESULTS: Of 27 patients who met study criteria, 19 (70%) were nonsurvivors and eight (30%) were survivors. The relative risk of death was 2.2 times greater in patients who exhibited the combination of pH less than 7.35 and a base deficit greater than 4 mEq/L, at any time in their ICU course, than in patients who did not (95% confidence interval = 1.01, 4.81). Furthermore, the relative risk of death was 3.7 times greater in patients who required positive end-expiratory pressure greater than 10 cm H2O after 96 hrs of ICU care than in those patients who did not (95% confidence interval = 1.09, 12.33). Indices of oxygen transfer, severity of chest radiograph abnormalities, concurrent lung infections, and most laboratory studies on hospital admission were not different between the two groups nor predictive of hospital survival. CONCLUSIONS: When dealing with AIDS/P. carinii pneumonia/ICU patients, it is not possible to distinguish who will survive to hospital discharge based on information routinely available before ICU admission. Those patients with the greatest chance of survival demonstrate a significant decrease in the required level of respiratory support within the first 4 days of ICU care. The presence of a metabolic acidemia (pH less than 7.35 and base deficit greater than 4 mEq/L), at any time during the ICU course, is a poor prognostic sign. We suggest that such objective variables should be included in the development of any new outcome predictor model for this group of ICU patients.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Airway pressure release ventilation in severe acute respiratory failure.

Airway pressure release ventilation (APRV), a new ventilatory support technique, was compared with conventional intermittent positive-pressure ventilation plus PEEP (CPPV) in 18 patients with severe acute respiratory failure. Patients were initially stabilized on CPPV and then switched to APRV. The APRV provided effective ventilatory support in 17 of 18 patients; APRV achieved similar levels of alveolar ventilation as CPPV (for APRV, mean PaCO2 = 45.0 +/- 6.2 mm Hg; vs for CPPV, mean PaCO2 = 43.3 +/- 5.7 mm Hg), with significantly lower mean maximum airway pressures (38.9 +/- 10.1 cm H2O vs 64.6 +/- 15.4 cm H2O; p = 0.0001) and mean VT (0.79 +/- 0.11 L vs 1.05 +/- 0.15 L; p = 0.0002). No significant differences in mean airway pressure, end-expiratory pressure, FIO2, ventilator rate, arterial blood gas levels, and hemodynamic function were noted between APRV and CPPV.

Acute Disease↗
PubMed1990

Comparing multiple RNA secondary structures using tree comparisons.

In a previous paper, an algorithm was presented for analyzing multiple RNA secondary structures utilizing a multiple string alignment algorithm. In this paper we present another approach to the problem of comparing many secondary structures by utilizing a very efficient tree-matching algorithm that will compare two trees in O([T1] X [T2] X L1 X L2) in the worst case and very close to O([T1] X [T2]) for average trees representing secondary structures. The result of the pairwise comparison algorithm is then used with a cluster algorithm to produce a multiple structure clustering which can be displayed in a taxonomy tree to show related structures.

Algorithms↗
PubMed1989

Detection of common motifs in RNA secondary structures.

We describe a novel computerized system for comparison of RNA secondary structures and demonstrate its use for experimental studies. The system is able to screen a very large number of structures, to cluster similar structures and to detect specific structural motifs. In particular, the system is useful for detecting mutations with specific structural effects among all possible point mutations, and for predicting compensatory mutations that will restore the wild type structure. The algorithms are independent of the folding rules that are used to generate the secondary structures.

Algorithms↗
PubMed1989

Preliminary evaluation of an intra-arterial blood gas system in dogs and humans.

The reliability and accuracy of an intra-arterial fluorescent optode system to measure continuously pHa, PaCO2, and PaO2 were evaluated in a dog model and in a group of critically ill patients. Six hundred sixty-three arterial blood gas (ABG) samples were analyzed for pHa, PaCO2, and PaO2 in the dog studies. The intra-arterial blood gas system (IBGS) indicated a steady state in 420 instances for pH, 359 instances for PaCO2, and 256 instances for PaO2. Comparison of these ABG and IBGS values by linear regression analysis revealed r = .97 for pHa, .95 for PaCO2, and .96 for PaO2. The mean +/- SD of the difference between ABG and IBGS was -0.02 +/- 0.03 for pHa, 1.05 +/- 3.8 for PaCO2, and -17 +/- 13 for PaO2. Nonsteady states were correctly identified by the IBGS in every instance. Comparisons between 79 temporally matched ABG and IBGS values, exclusive of in vivo calibration samples, in 12 critically ill patients revealed r = .97 for pHa, .96 for PaCO2, and .99 for PaO2. The difference was 0.002 +/- 0.02 for pHa, 0.44 +/- 2.97 for PaCO2, and -1.22 +/- 9.34 for PaO2. We conclude that it is possible to measure continuously pHa, PaCO2, and PaO2 with the IBGS in critically ill patients for periods from 3 to 25.5 h while maintaining the ability to monitor BP and withdraw blood samples from the arterial cannula. Agreement between the two techniques is within clinically acceptable ranges for pHa and PaCO2, whereas PaO2 measurement by the IBGS requires further refinement.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗