Biomedical subjects

R F Goldstein

Publications and source records attributed to R F Goldstein.

11 recordsLinked to original sources

PubMed1995

Influence of acidosis, hypoxemia, and hypotension on neurodevelopmental outcome in very low birth weight infants.

OBJECTIVE: We previously demonstrated that acidosis (pH < 7.15) predicts poor motor outcome in very low birth weight (VLBW) infants. The present study was undertaken to examine the association between acidosis and developmental outcome in more detail and to better understand the interrelationship of acidosis with related factors such as hypoxemia and hypotension. METHODS: The nursery records of 191 infants enrolled in our VLBW follow-up study were reviewed to identify the type of acidosis (metabolic or respiratory) present, measure the duration of single and cumulative episodes, and examine the interaction of acidosis with hypoxemia and hypotension. The Bayley Scales of Infant Development and a detailed neurologic examination were performed at 6 (n = 158) and 24 (n = 106) months corrected age. RESULTS: At 6 months, both respiratory and metabolic acidosis as well as the total duration and longest single episode of acidosis were significantly correlated with cognitive, motor, and neurologic outcome (P < .0001). By 24 months, only the association of the metabolic component of acidosis with all three outcome measures remained significant. Duration of hypotension independently correlated with outcome at both testing periods (P < .002) but isolated hypoxemia did not. The metabolic component of acidosis and isolated hypotension contributed significantly to the variance in all three outcome measures (P < .05). Duration of hypoxemia, but not hypotension, contributed significantly (53%) to the variance in the metabolic component of acidosis. CONCLUSION: We conclude that it is the metabolic component of acidosis that is important in predicting poor developmental outcome in VLBW infants. The detrimental effect of hypoxemia appears to be closely related to the occurrence of metabolic acidosis while hypotension has an independent effect on outcome.

Acidosis↗

PubMed1992

Studies of DNA dumbbells. I. Melting curves of 17 DNA dumbbells with different duplex stem sequences linked by T4 endloops: evaluation of the nearest-neighbor stacking interactions in DNA.

Seventeen DNA dumbbells were constructed that have duplex sequences ranging in length from 14 to 18 base pairs linked on the ends by T4 single-strand loops. Fifteen of the molecules have the core duplexes with the sequences 5'G-T-A-T-C-C-(W-X-Y-Z)-G-G-A-T-A-C3', where (W-X-Y-Z) represents a unique combination of A.T, T.A, G.C, and C.G base pairs. The remaining two molecules have the central sequence (W-X-Y-Z) = A-C and A-C-A-C-A-C. These duplex sequences were designed such that the central sequences include different combinations of the 10 possible nearest-neighbor (n-n) stacks in DNA. In this sense the set of molecules is complete and serves as a model system for evaluating sequence-dependent local stability of DNA. Optical melting curves of the samples were collected in 25, 55, 85, and 115 mM [Na+], and showed, regardless of solvent ionic strength, that the transition temperatures of the dumbbells vary by as much as 14 degrees for different molecules of the set. Results of melting experiments analyzed in terms of a n-n sequence-dependent model allowed evaluation of nine independent linear combinations of the n-n stacking interactions in DNA as a function of solvent ionic strength. Although there are in principle 10 possible different n-n interactions in DNA, these 10 are not linearly independent and therefore can not be uniquely determined. For molecules with ends, there are 9 linearly independent combinations, as opposed to circular or semiinfinite repeating copolymers where only 8 linear combinations of the 10 possible n-n interactions are linearly independent. The n-n interactions are presented as combinations of the deviations from average stacking for the 5'-3' base-pair doublets, delta Gi, and reveal several interesting features: (1) Titratable changes in the values of delta Gi with changing salt environment are observed. In all salts the most stable unique combination is delta G4 = (delta GGpC+delta GCpG)/2, and the least stable is the GpG/CpC stack, delta G2 = delta GGpG/CpC. (2) The chi 2 values of the fits of the evaluated delta Gi's to experimental data increased with decreasing [Na+], suggesting that significant interactions beyond nearest neighbors become more pronounced, particularly at 25 nM Na+.(ABSTRACT TRUNCATED AT 400 WORDS)

Base Sequence↗

PubMed1992

How many numbers are required to specify sequence-dependent properties of polynucleotides?

There are 10 unique dinucleotides of double-stranded DNA, but only 8 independent nearest-neighbor energies that occur in circular DNA, as shown by D. M. Gray and I. Tinoco [(1970) Biopolymers 9, 223-244]. We extend that analysis to include end effects, and show that the number of unique dinucleotide pairs (including ends) is 14, but there are only 12 independent energies. We discuss how these 12 energies (or spectra or any other pairwise additive property) can be measured and displayed, and how they should and should not be compared between experimenters. As an example, we analyzed the recently reported melting curves [M.J. Doktycz et al. (1992) Biopolymers, 32, 849-864.] of 16 DNA dumbbells in two different Na+ environments. This analysis reveals a new means for evaluating end effects and the emergence of longer than nearest-neighbor interactions at low salt concentration.

Base Composition↗

PubMed1991

Nursery Neurobiologic Risk Score: important factor in predicting outcome in very low birth weight infants.

We developed a nursery Neurobiologic Risk Score (NBRS) based on potential mechanisms of brain cell injury in preterm infants and correlated it with developmental outcome at the corrected ages of 6, 15, and 24 months. The NBRS was determined at 2 weeks of age and at the time of discharge from intensive care in 58 preterm infants with birth weights less than or equal to 1500 gm. The NBRS correlated significantly with the Bayley Scales of Infant Development, Mental Development Index (MDI) (r = -0.61 to -0.40) and Psychomotor Development Index (PDI) (r = -0.59 to -0.46), and with abnormal neurologic examination findings (r = 0.59 to 0.73) at the three testing periods. Although 12 of the 13 items composing the NBRS individually correlated with one or more outcome variables, seven items (infection, blood pH, seizures, intraventricular hemorrhage, assisted ventilation, periventricular leukomalacia, and hypoglycemia) accounted for almost all of the explained variance. Logistic regression of individual items demonstrated intraventricular hemorrhage to be the most important item for predicting the MDI at 24 months; pH was the most influential item for predicting the PDI at every testing period. A shorter, revised NBRS that included only the seven significant items demonstrated as strong a correlation with developmental outcome as the original NBRS. A revised 2-week score of greater than or equal to 5 or a discharge score of greater than or equal to 6 demonstrated 100% specificity and had a 100% positive predictive value for an abnormal outcome at 24 months of age in this group of infants. We conclude that the NBRS identifies during the intensive care nursery stay those infants at highest risk for an abnormal outcome related to nursery events. In addition, analysis of NBRS items provides insight into the relative importance of individual factors for influencing mental, motor, and neurologic outcome.

Brain Damage, Chronic↗

PubMed1991

Narcotic sedation stabilizes arterial blood pressure fluctuations in sick premature infants.

Blood pressure (BP) fluctuations in infants with respiratory distress syndrome (RDS) are related to spontaneous respirations and have been associated with an increased incidence of intraventricular hemorrhage. Both initiation of mechanical ventilation in the nonventilated infant and muscle paralysis in the ventilated infant can help stabilize these fluctuations. We hypothesized that narcotic sedation would also be effective in decreasing BP fluctuations when pharmacologic intervention is deemed necessary. Twenty premature infants were paralyzed with pancuronium or sedated with morphine or fentanyl for clinical indications. Blood pressure and respiratory tracings before and after medication were analyzed for average peak systolic BP (SBP) and the percentage of spontaneous respirations (SResp). Fluctuations of SBP were quantitated using the coefficient of variation (CV). A marked reduction was found in both CV and SResp following administration of all three drugs. Peak inspiratory pressure and ventilator rate were increased in the pancuronium group. In 7 out of 14 patients in whom spontaneous respirations persisted following sedation, there was a strong association between the percentage of decrease in CV and SResp. Advantages of narcotic sedation over muscle paralysis are discussed.

Blood Pressure↗

PubMed1990

EQUIL: simulation and data analysis of binding reactions with arbitrary chemical models.

We have developed an algorithm for simulation and analysis of arbitrary chemical systems in equilibrium, with emphasis on ligand binding reactions. The program EQUIL can treat reactions involving multiple ligands, multiple binding sites, ternary complex models, allosteric effectors, competitive and noncompetitive binding, conformational changes, cooperativity, and generally any scheme that can be represented as a set of chemical equations. EQUIL is based on a general thermodynamic model of chemical equilibria; it does not involve nonlinear transformation of experimental data, but it does require the user to define the model of interaction between ligands and receptors by writing down the appropriate chemical reactions. EQUIL contains features of particular importance to ligand binding experiments: variable binding capacities, nonspecific binding, and the ability to simultaneously analyze data from different types of experiments. Furthermore, the simulation feature of EQUIL allows the user to investigate the feasibility of experiments that could possibly distinguish between different reaction models. We illustrate the use of this program on personal computers to analyze and simulate simple and complicated interactions between ligands and receptors.

Algorithms↗

PubMed1990

Fluctuations of arterial blood pressure decrease with mechanical ventilation in premature infants with respiratory distress syndrome.

Marked fluctuations of arterial blood pressure (ABP) are associated with an increased risk of intraventricular hemorrhage. The pathophysiology is linked to spontaneous breathing. We hypothesized that these fluctuations would decrease after initiation of effective mechanical ventilation. We studied 20 infants treated with nasal continuous positive airway pressure (CPAP) and oxygen for early respiratory distress. Eleven required intubation for clinical indications. Simultaneous ABP and respiratory tracing obtained before and following intubation were analyzed for average peak systolic blood pressure (SBP) and the percentage of spontaneous respirations (SResp). Fluctuations of SBP were quantitated using the coefficient of variation (CV). The remaining 9 infants with minimal lung disease served as a control group. There was a small increase in SBP, and a marked decrease in both CV and SResp following intubation. A significant correlation was found between the percent decreases in CV and SResp. We conclude that beat-to-beat fluctuations of ABP decrease after the initiation of effective mechanical ventilation. This effect is primarily due to a decrease in spontaneous breathing.

Blood Pressure↗

PubMed1986

Cooperative polymerization reactions. Analytical approximations, numerical examples, and experimental strategy.

How does one obtain kinetic rate constants from the time course of a reversible and cooperative polymerization reaction? We examine a simple version of the homogeneous nucleation-elongation model with both analytical and numerical techniques to test some common assumptions and develop an experimental strategy. The assumption of irreversible polymer formation is found to be a useful and adequate approximation for the numerical determination of monomer disappearance. The assumption of early "pre-equilibrium" between monomer and seed, however, is shown numerically and analytically to produce significant errors over a wide range of parameters, particularly for small seed lengths. We exhibit numerical solutions for many different parameters, and also discuss analytical techniques that allow approximate solutions for several conditions: the high-concentration limit; the long-time limit; and the long-seed-length, lows concentration limit. The overall reaction simplifies when the monomer concentration is large. An experimental strategy for elucidating the seed size and the rate constants for polymerization and depolymerization is presented.

Biopolymers↗

PubMed1985

Do vibrational spectroscopies uniquely describe protein dynamics? The case for myoglobin.

We develop a quasi-harmonic description of protein dynamics and apply this description to the anomalous Mössbauer, infrared, x-ray diffraction, and EXAFS (extended x-ray absorption fine structure spectroscopy) data that are available for myoglobin (Mb) and its interactions with carbon monoxide (CO). In the quasi-harmonic approximation the dynamical parameters derived from these spectroscopic data are relevant in the calculation of reaction rates, and we give a quantitative description of the nonexponential kinetics of Mb-CO binding observed at low temperatures. All these data have previously been interpreted in terms of the more complex conformational substates model for protein dynamics. We point out several problems with this model and propose experiments that can provide detailed tests of the quasi-harmonic theory proposed here.

Iron↗

PubMedDate not supplied

Effect of endotracheal continuous positive airway pressure on sensitivity to carbon dioxide and on respiratory timing in preterm infants.

To determine the effects of continuous positive airway pressure (CPAP) on ventilatory response to CO2 and inspiratory and expiratory duration in preterm infants, 24 preterm infants with an average birth weight of 1220 g were studied at a mean age of 10.6 days. CPAP was applied via an uncuffed endotracheal tube. Testings were performed between ambient pressure and a positive airway pressure of 10 cm H2O. Approximately 2/3 of the applied pressure was transmitted to the esophagus. All infants demonstrated a ventilatory response to carbon dioxide of less than 50 ml/min per mm Hg Pco2 at ambient pressure, and no infant showed significant improvement at increasing levels of CPAP. Drive to breathe, as reflected in the inspiratory flow rate (Vt/Ti) also failed to change significantly. It may be concluded that in the apparent absence of significant changes in lung volume, CPAP fails to increase sensitivity to CO2 in preterm infants recovering from hyaline membrane disease.

Carbon Dioxide↗

PubMedDate not supplied

Dynamic light scattering investigations of RecA self-assembly and interactions with single strand DNA.

Dynamic light scattering (DLS) measurements were performed on self-assembled solutions of RecA as a function of assembly time under strand exchange ionic strength conditions (10 mM MgCl2, 65 mM NaCl, 10 mM Tris-HCl, pH = 7.5, 1 mM DTT, 3-4 microM RecA) in the absence of ATP. These measurements yield distributions of the translational diffusion coefficients of the changing populations of assembling protein species. Interpretations of results of DLS measurements are made in terms of model hydrodynamic calculations that indicate, under the solution conditions employed, the smallest fundamental quaternary subunit of RecA is a hexamer in a toroidal or lock-washer configuration. Interactions of M13mp19 circular single strand DNA (ssDNA) with RecA assembled to different stages were also investigated. Additions of ssDNA to self-assembled solutions of RecA acts to dissociate the associated structures into hexamer subunits. However, the effect of ssDNA on assembled RecA is highly dependent on the RecA self-assembly state. The longer the assembly time, the less reversible the self-assembled structures of RecA become. Binding isotherms of titrated mixtures of ssDNA with RecA self-assembled to various stages were also determined. Evaluated dissociation constants of RecA/ssDNA complexes were found to increase with increases of the associated state of RecA. These results strongly suggest that, under the solvent conditions employed, the active ssDNA binding form of RecA is a hexamer.

Adenosine Triphosphate↗