Biomedical subjects

R F Goldstein

Publications and source records attributed to R F Goldstein.

At least 19 recordsLinked to original sources

PubMed1999

Studies of DNA dumbbells VII: evaluation of the next-nearest-neighbor sequence-dependent interactions in duplex DNA.

Melting experiments were conducted on 22 DNA dumbbells as a function of solvent ionic strength from 25-115 mM Na(+). The dumbbell molecules have short duplex regions comprised of 16-20 base pairs linked on both ends by T(4) single-strand loops. Only the 4-8 central base pairs of the dumbbell stems differ for different molecules, and the six base pairs on both sides of the central sequence and adjoining loops on both ends are the same in every molecule. Results of melting analysis on the 22 new DNA dumbbells are combined with our previous results on 17 other DNA dumbbells, with stem lengths containing from 14-18 base pairs, reported in the first article of this series (Doktycz, Goldstein, Paner, Gallo, and Benight, Biopoly 32, 1992, 849-864). The combination of results comprises a database of optical melting parameters for 39 DNA dumbbells in ionic strengths from 25-115 mM Na(+). This database is employed to evaluate the thermodynamics of singlet, doublet, and triplet sequence-dependent interactions in duplex DNA. Analysis of the 25 mM Na(+) data reveals the existence of significant sequence-dependent triplet or next-nearest-neighbor interactions. The enthalpy of these interactions is evaluated for all possible triplets. Some of the triplet enthalpy values are less than the uncertainty in their evaluation, indicating no measurable interaction for that particular sequence. This finding suggests that the thermodynamic stability of duplex DNA depends on solvent ionic strength in a sequence-dependent manner. As a part of the analysis, the nearest-neighbor (base pair doublet) interactions in 55, 85, and 115 mM Na(+) are also reevaluated from the larger database.

Base Sequence↗

PubMed1999

Infant arousal in an en-face exchange with a new partner: effects of prematurity and perinatal biological risk.

Very low birth weight (VLBW) infants of higher (n = 18) and lower (n = 29) perinatal biological risk were contrasted at 4 months adjusted age with healthy full-term infants (n = 32) in their arousal during a standardized peekaboo game with an examiner. VLBW infants showed less positive arousal, more negative arousal, and 3 mixtures of behavioral cues across the peekaboo game seldom seen for full-term infants-strong cues of both positive and negative arousal, strong cues of negative arousal alone, and no strong cues of either positive or negative arousal. Contrary to expectations, perinatal biological risk did not strongly predict variations in arousal within the VLBW group. Possible changes in how internal and external sources of arousal are integrated provide one explanation for the presence of strong relationships between perinatal biological risk and social responsiveness near term age and their disappearance by 4 months of age.

Analysis of Variance↗

PubMed1997

Is size discordancy an indication for delivery of preterm twins?

OBJECTIVE: Our goal was to determine the clinical significance of size discordancy in preterm twins. STUDY DESIGN: A retrospective study was performed to review outcomes of twins delivered between Jan. 1, 1988, and June 30, 1995. Maternal and neonatal records were assessed for demographic data, maternal medical history, and neonatal mortality and morbidity outcomes. Discordancy was defined as > or = 20% difference in birth weight. The chi 2 analysis was performed. RESULTS: There were 42 sets of discordant twins and 77 sets of concordant twins in the final analysis. The distribution of gestational ages in both groups was similar. We found no difference in maternal morbidity between the groups. Discordant sets had a significantly longer hospital stay (p = 0.003) and more cases of hyperbilirubinemia (p = 0.01), but there were no other differences in morbid outcomes. There were no differences in outcome variables between the two twins within discordant sets with respect to gender, size, birth order, growth restriction, or route of delivery. There were no stillbirths among any of the 238 infants. Of the 15 neonatal deaths, none occurred in infants delivered after 32 weeks' gestation or in infants weighing > 2000 gm at birth. Infants who were small for gestational age had a higher incidence of sepsis (p = 0.043) and longer hospital stays (p = 0.005) compared with infants who were appropriate for gestational age. CONCLUSIONS: Size discordancy alone does not appear to be an indication for preterm delivery of twins. When results of antenatal testing are normal and growth restriction is absent, attempts should be made to achieve a gestational age > 32 weeks and weight > 2000 gm before delivery is considered.

Adolescent↗

PubMed1997

Developmental outcome of very low birth weight infants at four years of age as a function of biological risk and psychosocial risk.

The continuing contribution of early biological and psychosocial risk factors to developmental outcome of 55 very low birth weight infants (< or = 1500 g) was assessed at 4 years of age. Biological risk, assessed by the Neurobiologic Risk Score, accounted for significant portions of the variance in the perceptual-performance (17%) and motor (35%) dimensions of the McCarthy Scales of Children's Abilities. Psychosocial risk, reflected in maternal appraisals of daily stress during the newborn period, did not account for a significant portion of variance in any of the McCarthy Scales. Maternal education level, however, another measure of psychosocial risk, accounted for significant portions of variance (from 6% to 34%) on each of the McCarthy Scales. Movement from low neurobiologic risk status to poor outcome status at 4 years of age was associated with a number of psychosocial variables, including maternal education and early levels of maternal daily stress. The findings are discussed in terms of early markers for very low birth weight infants who require careful follow-up and of potential intervention targets to promote developmental outcome.

Brain Damage, Chronic↗

PubMed1996

Cerebral blood flow and carbon dioxide reactivity in neonates during venoarterial extracorporeal life support.

OBJECTIVES: a) To determine if cerebral blood flow is symmetric after internal carotid artery and ipsilateral internal jugular vein ligation in infants during venoarterial extracorporeal life support. b) To determine the cerebral CO2 reactivity (delta cerebral blood flow/delta torr CO2) of neonates during venoarterial extracorporeal life support and its correlation to neurodevelopmental outcome. DESIGN: Prospective, clinical study. SETTING: University hospital pediatric intensive care unit. PATIENTS: Fourteen neonates with respiratory failure who were receiving venoarterial extracorporeal life support. INTERVENTIONS: PaCO2 was altered by adjusting the CO2 gas flow through the membrane oxygenator. Cerebral blood flow was measured over both parietal-temporal regions at three PaCO2 values using xenon-133 clearance methodology. Cerebral blood flow measurements were made early (< or = 12 hrs of extracorporeal life support, n = 10) or late (> or = 48 hrs of extracorporeal life support, n = 10). In six of 14 infants, both early and late cerebral blood flow rates were measured. PaO2, mean arterial pressure, pump flow rate, and temperature were stable during each study period. Neurodevelopmental outcome was assessed in the neonatal follow-up clinic. MEASUREMENTS AND MAIN RESULTS: Right and left hemispheric cerebral blood flow rates were significantly correlated with each other during early and late extracorporeal life support (p = .0001; r2 = .91). Overall, hemispheric cerebral blood flow was statistically symmetric. There was no association of CO2 reactivity (delta cerebral blood flow/delta torr PCO2, range 0.04 to 1.36 mL/min/100 g/torr) with short-term neurodevelopmental outcome. Infants with normal neurodevelopmental outcome had variable CO2 reactivity (range 0.04 to 0.67 mL/min/100 g/torr). Normal short-term neurodevelopmental outcome was observed in two infants with cerebral blood flow of < 10 mL/min/100 g. CONCLUSIONS: Hemispheric cerebral blood flow was symmetric in infants during early and late venoarterial extracorporeal life support. Some subgroups showed a trend toward decreased right hemispheric cerebral blood flow, but the small number of patients limited interpretation of this finding. CO2 reactivity and cerebral blood flow were highly variable in this population, and were not predictive of short-term neurodevelopmental outcome. Stressed neonates with extremely low cerebral blood flow rates may have relatively normal short-term neurodevelopmental outcome after venoarterial extracorporeal life support.

Blood Pressure↗

PubMed1996

Delayed development of sensorineural hearing loss after neonatal hyperbilirubinemia: a case report with brain magnetic resonance imaging.

Sensorineural hearing loss has long been known to be a clinical consequence of kernicterus. Brainstem auditory evoked potentials (BAEPs) that occur in hyperbilirubinemic infants, can be reversed in the neonatal period by exchange transfusion. The case was reported in an infant with neonatal hyperbilirubinemia from hemolysis due to glucose-6-phosphate dehydrogenase (G6PD) deficiency and napthalene exposure. BAEPs showed that the baby had normal hearing at 30 decibels at 13 days of age, after exchange transfusions, but had developed profound bilateral sensorineural hearing loss by 7 months of age. The brain magnetic resonance imaging (MRI) findings at 7 months are also presented.

Cochlea↗

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↗

PubMed1994

Efficient rotamer elimination applied to protein side-chains and related spin glasses.

Folded proteins and spin glasses share various properties, such as seemingly random interactions between residues (spins), and one might presume that some generic behaviors of spin glasses would also be exhibited in a general way by proteins. But a comparison here shows that the side-chain conformation systems of apo-myoglobin and lysozyme are qualitatively different from specific closely related spin glass systems. This difference is manifest in the number of rotamers that can be identified as definitely not contributing to the global energy minimum. This identification is effected by using a significantly enhanced version of the Dead End Elimination theorem (Desmet, J., M. De Maeyer, B. Hazes, and I. Lasters. 1992. The dead-end elimination theorem and its use in protein side-chain positioning. Nature. 356:539-542), which is much more effective and efficient in eliminating rotamers. In several cases (for proteins, although not for spin glasses) this improved Dead End Elimination theorem succeeded in identifying the absolute global minimum of rotamer conformations, with no statistical uncertainty. The difference between protein and spin glass is due to correlations between the interactions of one residue pair with another pair, and probably will play an important role in the thermodynamic behavior of the protein system.

Algorithms↗

PubMed1994

Developmental outcome of very low birth weight infants as a function of biological risk and psychosocial risk.

The relative contribution of biological and psychosocial risk factors to developmental outcome of 102 very low birth weight infants (< 1500 g) was delineated through 24 months corrected age. Biological risk, assessed by the Neurobiologic Risk Score (NBRS), accounted for significant amounts of variance in Bayley Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) at the 6-, 15-, and 24-month assessment points. Psychosocial risk, reflected in maternal appraisals of daily stress, accounted for a significant increment in cognitive outcome (MDI), over and above that accounted for by the NBRS, at each assessment point. Cognitive functioning at each assessment point differed as a function of biological risk and psychosocial risk status. The findings are discussed in terms of maternal stress as a marker of, and salient intervention target for, caregiving environments that can maximize or minimize the effects of biological vulnerability.

Brain Damage, Chronic↗

PubMed1993

Nursery neurobiologic risk score: levels of risk and relationships with nonmedical factors.

This study compares the Neurobiologic Risk Score (NBRS) with developmental outcome in 199 infants < or = 1500 g birth weight to determine levels of risk and to investigate the relative contributions of the NBRS and nonmedical factors to developmental outcome. The NBRS correlated significantly (p < .0001) with the Bayley Mental (MDI) and Psychomotor (PDI) Indexes, and neurologic examination score (NS) at 6, 15, and 24 months. Three risk groups were identified: low, NBRS < or = 4; intermediate, NBRS 5 to 7; and high, NBRS > or = 8 with an incidence of major handicaps at 24 months of 7%, 32%, and 50%, respectively. Of eight factors considered, the NBRS accounted for the greatest variance: MDI, 14 to 27%; PDI, 25 to 29%; NS, 34 to 42%. Additional increments of variance were contributed by gender (MDI, PDI, NS), maternal intelligence and race (MDI), and maternal education (PDI). The NBRS is a useful tool for identifying risk for developmental abnormalities due to neonatal medical events.

Birth Weight↗

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↗