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PubMed2001

Attenuated total reflection-Fourier transform infrared spectroscopy as a possible method to investigate biophysical parameters of stratum corneum in vivo.

We investigated the use of attenuated total reflection-Fourier transform infrared spectroscopy as a method to study differences in the molecular components of human stratum corneum in vivo. These variations as a function of the anatomic site and of the depth into its layered structure are important to understand the biology and physiology of the tissue. In this preliminary study we have investigated spectroscopic changes in 18 healthy individuals. Total reflection-Fourier transform infrared spectroscopy represents a potentially powerful tool to study biophysical properties of surfaces. We observed that, in vivo, biophysical parameters of the stratum corneum (such as hydration, lipid composition, and conformation of the aliphatic chains) are indeed dependent on the anatomic site. As in total reflection-Fourier transform infrared spectroscopy experiments the penetration depth of the evanescent field into the stratum corneum is comparable with the thickness of a layer of corneocytes, this technique can be used to follow the distribution of lipids, water, and proteins as a function of depth into the tissue. We found that, in vivo, these molecular components are non-uniformly distributed, in agreement with the presence of water and lipid reservoirs as observed with ex vivo ultrastructural investigations. Composition and conformational order of lipids are also a function of depth into the stratum corneum. Finally we compared the in vivo superficial hydration measured using the infrared absorption of the OH stretch of water, with the hydration measured using the Skicon hygrometer. Our results indicate that total reflection-Fourier transform infrared spectroscopy might be useful to measure important chemical and biophysical parameters of stratum corneum in vivo.

Adult↗
PubMed2006

The use of biophysical methods increases success in obtaining liganded crystal structures.

In attempts to determine the crystal structure of small molecule-protein complexes, a common frustration is the absence of ligand binding once the protein structure has been solved. While the first structure, even with no ligand bound (apo), can be a cause for celebration, the solution of dozens of apo structures can give an unwanted sense of déjà vu. Much time and material is wasted on unsuccessful experiments, which can have a serious impact on productivity and morale. There are many reasons for the lack of observed binding in crystals and this paper highlights some of these. Biophysical methods may be used to confirm and optimize solution conditions to increase the success rate of crystallizing protein-ligand complexes. As there are an overwhelming number of biophysical methods available, some of the factors that need to be considered when choosing the most appropriate technique for a given system are discussed. Finally, a few illustrative examples where biophysical methods have proven helpful in real systems are given.

Amino Acid Sequence↗
PubMed1989

In vivo biological validation and biophysical modeling of the sensitivity and positive accuracy of endocrine peak detection. I. The LH pulse signal.

The false positive (type I) and false negative (type II) errors inherent in computerized peak detection algorithms can have a major impact on the valid interpretation of physiological experiments. To objectively define the nature and extent of statistical errors associated with the identification of episodic gonadotropin (LH) peaks, we have employed two complementary approaches. First, using a general biophysical model for simulating episodic LH secretion, we have estimated optimal pulse analysis parameters that yield maximal sensitivity (probability of finding any given peak) and positive accuracy (probability that any identified peak is a true pulse) in synthetic LH series approximating those observed spontaneously in vivo. Secondly, we have estimated optimal peak detection parameters in an in vivo primate animal model, in which electrophysiological correlates of spontaneous LH pulses were documented independently by continuous electrophysiological monitoring of medial basal hypothalamus multiunit activity. These combined approaches indicate that LH time series can be analyzed for episodic LH pulsatility by an appropriately constrained, objective computerized algorithm with minimal false negative and false positive errors, i.e. with resultant high sensitivity and positive accuracy. Moreover, optimal pulse analysis parameters exhibited similar sensitivity and positive accuracy rates in both the biophysical simulations and the animal model. Thus, we suggest that the combined use of an algebraically explicit biophysical simulation model and an in vivo animal paradigm may serve to clarify the nature and extent of false negative and false positive errors in the detection of other hormone peaks as well as the gonadotropin LH.

Animals↗
PubMed2006

Biophysical mechanisms: a component in the weight of evidence for health effects of power-frequency electric and magnetic fields.

Comparatively high exposures to power-frequency electric and magnetic fields produce established biological effects that are explained by accepted mechanisms and that form the basis of exposure guidelines. Lower exposures to magnetic fields (< 1 microT average in the home) are classified as "possibly carcinogenic" on the basis of epidemiological studies of childhood leukemia. This classification takes into consideration largely negative laboratory data. Lack of biophysical mechanisms operating at such low levels also argues against causality. We survey around 20 biophysical mechanisms that have been proposed to explain effects at such low levels, with particular emphasis on plausibility: the principle that to produce biological effects, a mechanism must produce a "signal" larger than the "noise" that exists naturally. Some of the mechanisms are impossible, and some require specific conditions for which there is limited or no evidence as to their existence in a way that would make them relevant to human exposure. Others are predicted to become plausible above some level of field. We conclude that effects below 5 microT are implausible. At about 50 microT, no specific mechanism has been identified, but the basic problem of implausibility is removed. Above about 500 microT, there are established or likely effects from accepted mechanisms. The absence of a plausible biophysical mechanism at lower fields cannot be taken as proof that health effects of environmental electric and magnetic fields are impossible. Nevertheless, it is a relevant consideration in assessing the overall evidence on these fields.

Animals↗
PubMed1980

Antepartum fetal evaluation: development of a fetal biophysical profile.

Five fetal biophysical variables, fetal breathing movements, fetal movements, fetal tone, qualitative amniotic fluid volume, and the nonstress test, were measured in the same observation period in 216 patients with high-risk pregnancies. All delivered within one week of the last observation. The relationship between individual biophysical variables and combinations of variables to the outcome of pregnancy as judged by five-minute Apgar score, fetal distress in labor, and perinatal mortality rate (PMN) was determined. For any single test, the false negative rate was low and was similar between tests, but the false positive rate was high (greater than 50%) and varied significantly between tests. Combining tests resulted in a significant change in both the false negative and false positive rates as compared to any single test. The most accurate differentiation of the normal from the compromised fetus was obtained when all five variables were studied. The PNM ranged from 0 when all variables were normal to 600 per 1,000 when all were abnormal. These data suggest that combined fetal biophysical testing is a more accurate method of antepartum fetal evaluation than any single method.

Adult↗
PubMed1988

Gestational age and fetal biophysical assessment.

With improved neonatal care, biophysical assessment to detect fetal asphyxia is used increasingly at an earlier gestational age. We have tested five fetal biophysical variables: nonstress test, fetal breathing movements, fetal movements, fetal tone, and amniotic fluid volume 11,012 times in 5582 singleton fetuses in whom there was a normal perinatal outcome. The nonstress test and fetal breathing movements were more likely to be abnormal at 26 to 33 weeks' gestation compared with 34 to 41 weeks. The nonstress test, fetal breathing movements, fetal tone, and amniotic fluid volume were more likely to be abnormal at 42 to 44 weeks' gestation compared with 37 to 41 weeks. Fetal biophysical tests should be interpreted in relation to gestational age.

Amniotic Fluid↗
PubMed1989

Effects of maternal hyperoxia on the biophysical assessment of fetuses with suspected intrauterine growth retardation.

Fifty-two third-trimester fetuses with suspected intrauterine growth retardation were studied by means of a computer-assisted biophysical assessment scheme, which used maternal hyperoxia as a diagnostic probe. Biophysical data examined included percentage of time spent in breathing, mean breath rate, and percentage of time spent in body movement during a 90-minute observation: 30-minute baseline, 15-minute hyperoxia, and 45-minute posthyperoxia. Mean baseline movement in fetuses found as neonates to have intrauterine growth retardation (N = 18) was significantly lower than that of normal fetuses (N = 34). Fetal body movements and breathing movements increased significantly after hyperoxia in the intrauterine growth retardation group but not in the normal group. Increases of more than 75% over baseline for fetal breathing and more than 250% over baseline for fetal body movements yielded a sensitivity of 56%, specificity of 94%, positive predicative value of 83%, and negative predicative value of 80%. Maternal hyperoxia during biophysical testing may improve the accuracy of detecting intrauterine growth retardation.

Female↗
PubMed1994

Endocrinologic and biophysical responses to prolonged (24-hour) hypoxemia in fetal goats.

OBJECTIVE: The purpose of this study was to observe some fetal endocrinologic and biophysical responses to prolonged (24-hour) nonacidemic hypoxemia in fetal goats. STUDY DESIGN: Endocrinologic and biophysical changes during continuous infusion of nitrogen into the maternal trachea were examined in six chronically instrumented goat fetuses at 123 to 131 days' gestation. We measured arginine vasopressin, adrenocorticotropic hormone, cortisol, epinephrine, and norepinephrine as endocrinologic parameters and fetal heart rate, fetal blood pressure, and fetal breathing movements as biophysical parameters. RESULTS: Fetal arterial PO2 declined from 25.1 +/- 2.1 mm Hg at baseline to 16.8 +/- 0.9 mm Hg at 1 hour of hypoxemia and remained at this level (p < 0.05). Arginine vasopressin, adrenocorticotropic hormone, and epinephrine initially rose in response to hypoxic stress, gradually declined, and by 24 hours were not significantly different from control values. Cortisol and norepinephrine remained significantly elevated through the experiments. Fetal breathing movements as a percentage of total time were 34.9% +/- 1.2% at baseline, 12.9% +/- 3.7% at 1 hour, and 70% to 80% of control values from 4 hours. Fetal heart rate was significantly reduced for the first 10 minutes, then progressively became tachycardiac thereafter. Systolic fetal blood pressure was significantly elevated for only 30 minutes. CONCLUSION: Arginine vasopressin, adrenocorticotropic hormone, and epinephrine of the endocrinologic parameters and fetal heart rate, fetal blood pressure, and fetal breathing movements are normalized during prolonged nonacidemic hypoxemia in fetal goats.

Adrenocorticotropic Hormone↗
PubMed1991

Human fetal mouthing movements: a potential biophysical variable for distinguishing state 1F from abnormal fetal behavior; report of 4 cases.

In late pregnancy, when fetal behavioural states are well developed, human fetuses spend about one third of their time in a quiescent state, 1F. In healthy fetuses biophysical tests often appear suboptimal if recording happens to occur in this state, and as a result prolonged recording may be necessary. We have examined fetal mouthing movements during state 1F in 65 fetuses beyond 36 weeks, with and without risk factors, but in whom there was no immediate evidence of compromise. We found that periodic rhythmical mouthing movements were a characteristic feature of state 1F, occurring in 93.0% of episodes, when the fetal mouth was visible. This compares favourably with variables of the biophysical profile, which were less likely to be satisfactory in state 1F - fetal breathing 53.8%, fetal movements 46.2%, fetal heart rate 69.2%, and overall biophysical score of 8 or 10, 60.0%. We identified objective evidence of fetal compromise (of various aetiologies) in four other fetuses of the same gestational age, and mouthing movements were absent in all four.

Adult↗
PubMed1991

Biochemical and biophysical characterization of the reovirus cell attachment protein sigma 1: evidence that it is a homotrimer.

The oligomerization state of the reovirus cell attachment protein sigma 1 (49K monomeric molecular weight) was determined by biochemical and biophysical means. Full-length (protein product designated A) and C-terminal truncated (protein product designated B) serotype 3 reovirus S1 mRNA transcripts synthesized in vitro were cotranslated in a rabbit reticulocyte lysate, and the products were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under conditions which allowed for the identification of oligomeric forms of sigma 1. A total of four oligomeric protein bands (corresponding to A3, A2B1, A1B2, and B3, respectively) was consistently observed, which suggests that the protein is made up of three monomeric subunits. Biophysical characterization of purified sigma 1 using column filtration and sucrose gradient sedimentation analysis confirmed the highly asymmetric shape of sigma 1 and allowed us to determine the molecular weight of the native protein to be approximately 132K (a trimer). Similar biophysical analysis on the two tryptic fragments of the sigma 1 [N-terminal fibrous tail (26K monomeric molecular weight) and the C-terminal globular head (23K monomeric molecular weight)] yielded molecular weights of 77K and 64K, respectively, both again corresponding to trimers. We therefore conclude that protein sigma 1 is a homotrimer and provide, with supportive experimental evidence, a rationale for the anomalous behavior of the oligomeric protein in SDS-polyacrylamide gels, which, coupled with chemical cross-linking studies, has in part led to the previous suggestion that sigma 1 might be a higher order oligomer.

Capsid Proteins↗
PubMed2005

Biophysical characterization of anionic lipoplexes.

Transfection efficiency of liposomal gene delivery vectors depends on an optimal balance in the electro-chemical and structural properties of the transfection-capable complexes. We have recently reported a novel anionic lipoplex DNA delivery system composed of a ternary complex of endogenous occurring non-toxic anionic lipids, physiological Ca2+ cations, and plasmid DNA encoding a gene of interest with high transfection efficiency and low toxicity. In this work, we investigate the electro-chemical and structural properties anionic lipoplexes and compare them with those of Ca2+-DNA complexes. Biophysical characterization is used to explain the transfection efficiency of anionic lipoplexes in mammalian CHO-K1 cells. Circular dichroism and fluorescence spectroscopy showed that the plasmid DNA underwent conformational transition from native B-DNA to Z-DNA due to compaction and condensation upon Ca2+-mediated complexation with anionic liposomes. Zeta potential measurements and gel electrophoresis studies demonstrated that Ca2+ interaction with plasmid DNA during the formation of lipoplexes also led to increased association of supercoiled plasmid DNA with the lipoplexes, leading to charge neutralization which is expected to facilitate transfection. However, even 10-fold higher concentrations of Ca2+ alone (in the absence of the anionic liposomes) were unable to induce these changes in plasmid DNA molecules. A model explaining the possible mechanism of anionic lipoplex formation and the correlation of high transfection efficiency to biophysical properties was proposed. These studies confirm the utility of biophysical studies to identify optimal formulation conditions to design efficient liposomal gene delivery vectors.

Anions↗
PubMed2007

Planning for sustainable tourism in southern Pulau Banggi: an assessment of biophysical conditions and their implications for future tourism development.

A priori assessments of a site's biophysical and socio-economic capacity for accommodating tourism are less common than tourism impact studies. A priori evaluations can provide a contextual understanding of ecological, economic and socio-cultural forces, which shape the prospects for sustainable tourism development at the host destination, and can avert adverse impacts of tourism. We conduct an a priori assessment of the biophysical environment of Pulau Banggi, in the Malaysian state of Sabah for sustainable tourism development. We characterise baseline conditions of the island's marine biodiversity, seasonality, and infrastructure. We then evaluate how existing biophysical conditions will influence options for sustainable tourism development. In particular, we suggest conditions, if there are any, which constitute a limit to future tourism development in terms of compatibility for recreation and resilience to visitor impacts. We find that the biggest constraint is the lack of adequate water and sanitation infrastructure. Blast fishing, although occurring less than once per hour, can potentially destroy the major attraction for tourists. We conclude that while Pulau Banggi possesses natural qualities that are attractive for ecotourism, financial and institutional support must be made available to provide facilities and services that will enable local participation in environmental protection and enhance prospects for future sustainable tourism.

Biodiversity↗
PubMed1984

The role of nonstress tests, fetal biophysical profile, and contraction stress tests in the outpatient management of insulin-requiring diabetic pregnancies.

Antepartum fetal surveillance methods applicable in a home glucose-monitored population of pregnant diabetic women have been evaluated. A testing sequence of nonstress heart rate testing, backed up by either the fetal biophysical profile or contraction stress testing employed at a twice weekly interval, in 107 outpatients was compared with the management of 140 historic control patients by weekly nonstress tests and daily plasma estriols. There were 617 of 672 (91.8%) reactive nonstress tests in outpatients compared to 566 of 626 (90.4%) reactive tests in hospitalized control patients. Of 13 contraction stress tests performed in the outpatient group, only one was positive. Although 2,670 estriol determinations were done on hospitalized control patients, none was used for outpatients. No losses were attributed to unexplained antenatal stillbirth in either group. A fetal biophysical score of 8 was found to be at least as reliable as a reactive nonstress test. Antenatal surveillance in the well-controlled, insulin-requiring diabetic woman can be safely achieved with a testing sequence that consists of twice weekly nonstress tests backed up by the fetal biophysical profile and contraction stress tests.

Diabetes Mellitus, Type 1↗
PubMed1987

The use of fetal biophysical profile improves pregnancy outcome in premature rupture of the membranes.

A protocol using daily fetal biophysical assessment was applied in 73 consecutive patients with premature rupture of the membranes and no clinical signs of infection or labor. A persistently low biophysical score (7 or less on two examinations 2 hours apart) in the presence of a nonreactive nonstress test and absence of fetal breathing was used as an indication for delivery. Measures of pregnancy outcome included the presence of amnionitis or neonatal infection. The outcome of pregnancy in this group of patients was compared with the outcomes of two historic groups: one managed conservatively (control group) and the other managed with amniocentesis on admission to the hospital (amniocentesis group). Infection outcome, maternal as well as neonatal, and low 5-minute Apgar scores were significantly less in the study than in the control group. The frequency of neonatal sepsis was significantly less in the study than in the amniocentesis group. These data suggest that management of premature rupture of the membranes with daily fetal biophysical profiles improves pregnancy outcome by reducing the incidence of maternal and neonatal infection.

Female↗
PubMed1994

Recovery of the ovine fetus from sustained hypoxia: effects on endocrine, cardiovascular, and biophysical activity.

OBJECTIVE: The purpose of this study was (1) to determine the ability of the ovine fetus to recover from a self-limiting asphyxial insult and (2) to monitor cardiovascular and biophysical activity as potential markers of such an insult or underlying neurologic impairment. STUDY DESIGN: Nineteen fetal sheep were studied (12 hypoxia and 7 control) at 0.9 of gestation during a 24-hour control period, up to 8 hours of either sustained hypoxemia or room air, and for a 40-hour recovery period. Fetal heart rate, blood pressure, electrocortical activity, electroocular activity, and breathing movements were monitored continuously. Fetal arterial blood was sampled at set times for blood gases, pH, lactate, and catecholamine levels. RESULT: Induced fetal hypoxemia resulted in a lactic metabolic acidosis that progressively worsened, with death occurring in three of the animals during the early recovery period. The remaining animals showed a rapid metabolic and endocrine normalization of values by 24 hours. Fetal cardiovascular and biophysical measurements likewise returned to control values during the early recovery period, although three animals had seizure-like activity. CONCLUSION: The near-term ovine fetus surviving a sustained asphyxial insult sufficient to induce neuropathologic change within the brain demonstrates a normalization of biophysical activity during the early period of recovery, although seizure-like activity may subsequently be evident.

Animals↗
PubMed1999

Fetal death after normal biophysical profile score: An eighteen-year experience.

OBJECTIVE: It was our goal to determine the false-negative rate of the biophysical profile, characterize an 18-year variation in the false-negative rate, examine the relationship between the last normal biophysical profile score and death, and compare the false-negative rate of 2 disparate populations. STUDY DESIGN: Biophysical profile scores of 86,955 patients at 2 medical centers were collected and recorded prospectively. All perinatal deaths occurring within 1 week of a normal score were similarly recorded. The annual false-negative rate, the cumulative false-negative rate, and the ratio of false-negative results in cases of subsequent fetal death to the perinatal mortality rate were calculated. RESULTS: There were 65 fetal deaths among 86,955 fetuses. Over an 18-year study period at one institution, the false-negative rate varied but not significantly. The cumulative false-negative rate was 0.708 per 1000 at one medical center studied and 2.289 per 1000 at the other center. The average interval between last normal score and fetal death was 3.62 days and did not vary significantly between the medical centers. CONCLUSIONS: False-negative results in cases of subsequent fetal death reflect events that are subsequent to the last normal test result. Fetomaternal hemorrhage was the single most identifiable fetal cause of false-negative results in cases of subsequent fetal death. The ratio of the false-negative rate in cases of subsequent fetal death to the perinatal mortality rate should be used as a more objective approach to reporting this value, because the false-negative rate likely reflects the underlying perinatal mortality.

False Negative Reactions↗
PubMed2000

Biophysical properties and responses to glutamate receptor agonists of identified subpopulations of rat geniculate ganglion neurons.

The goal of the current study was to evaluate the electrophysiological properties and responses to glutamate receptor agonists of rat geniculate ganglion (GG) neurons innervating the tongue. Subpopulations of GG neurons were labeled by injecting Fluoro-Gold (FG) or True Blue chloride into the anterior tongue and soft palate (AT and SP neurons) and applying FG crystals to the posterior auricular branch of the facial nerve (PA neurons). Three to 12 days later, the GG neurons were acutely isolated and patch clamped. Although many biophysical properties of the AT, SP and PA neurons were similar, significant differences were found among these groups in properties related to cell excitability. For example, the average amount of current necessary to elicit an action potential was 61 pA in AT neurons (n=55), 90 pA in SP neurons (n=41) and 189 pA in PA neurons (n=35, P<0.001). In addition, AT neurons tended to fire significantly more action potentials during depolarization as well as following hyperpolarizing pulses than SP or PA neuron types. Most GG neurons responded to application of glutamate receptor agonists. The neurons responded with a depolarization accompanied by a reduction in input resistance. These results suggest that subpopulations of neurons in the geniculate ganglion have distinct biophysical properties and express functional glutamate receptors. The differing biophysical properties of GG neurons is possibly related to their functional heterogeneity and glutaminergic neurotransmission may function in the processing of gustatory, and other sensory information, within the geniculate ganglion and its projections.

Action Potentials↗
PubMed1998

A simplified fetal biophysical profile.

OBJECTIVE: To modify the classic fetal biophysical profile (FBP) with the aim of obtaining rapid and accurate information about actual fetal condition in non-compromised fetuses with a subsequent favorable outcome and to be suitable for a number of outclinic patients. METHODS: Four-hundred and ninety-four fetuses from singleton pregnancies in two randomized groups were monitored by the modified FBP (mFBP) and 168 of them after the external vibratory acoustic stimulation (VAS/mFBP). The mFBP was characterized by two main characteristics: non-stress test was excluded and the testing was finished at the moment when all of the three fetal biophysical activities became normal. The external VAS was applied only in cases with no evidence of fetal activity at the start of the FBP. RESULTS: Of the examined fetuses, 326 fetuses in the control group were monitored by the mFBP and there were 316 (96.9%) favorable outcomes and 10 (3.1%) adverse perinatal outcomes. The sensitivity, specificity and positive and negative predictive values of the mFBP score in predicting adverse perinatal outcome were 60, 99, 66.7 and 98.7%, respectively. In the study group of 168 fetuses there were 165 (98.2%) favorable outcomes and three (1.8%) adverse perinatal outcomes. The sensitivity, specificity and positive and negative predictive values of the VAS/mFBP were 66.7, 100, 100 and 99.4%, respectively. The efficiency of the VAS/mFBP in predicting perinatal mortality alone was even higher. After the external VAS and the first 5 min of the modified testing approximately two-fifths (41.8%) of healthy fetuses with a subsequent good outcome exhibited normal in all of the three biophysical activities and approximately two-thirds (65.5%) of them after 10 min. In the VAS/mFBP group of healthy fetuses, during the same time periods, normal breathing movements were observed in 72% and 87% of fetuses, respectively. CONCLUSIONS: According to our results the mFBP and particularly the VAS/mFBP antenatal protocol as a new and rational variant of the FBP could improve fetal assessment allowing in cases of non-compromised fetuses rapid and accurate information about actual fetal well-being. Because of its high accuracy and a reduced testing time the antepartal method with observation of fetal breathing movements after VAS is becoming acceptable as a screening of fetal well-being evaluation in outclinic conditions.

Acoustic Stimulation↗