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PubMed2005

Specific issues after extracardiac fontan operation: ventricular function, growth potential, arrhythmia, and thromboembolism.

BACKGROUND: The purpose of this study was to define the prevalence of specific sequelae after extracardiac Fontan operation. METHODS: Sixty-five consecutive patients undergoing extracardiac Fontan operation were studied for mortality, Fontan failure, systemic ventricular function, supraventricular arrhythmias, thromboembolism, and growth potential. Age was 3 to 31 years (mean +/- standard deviation, 9.4 +/- 1.8; median, 7 years). The conduits were constructed of polytetrafluoroethylene (n = 50), and "viable" in situ pericardium (n = 15). The patients underwent serial echocardiogram, dynamic radionuclide studies, and cardiac catheterization. RESULTS: Operative mortality was 3%, and the incidence of conduit thrombosis was 4.6%. There was paradoxic filling of the right lung after femoral injection of the radiotracer in all cases of conduit obstruction. Perioperative and late postoperative supraventricular arrhythmias were observed in 9.2% and 4.7% of patients, respectively. Risk factors for supraventricular arrhythmias included systemic ventricular dysfunction (p = 0.000), heterotaxy syndrome (p = 0.008), systemic venous anomalies (p = 0.015), and previous bidirectional Glenn operation (p = 0.017). At a mean follow-up of 77 +/- 2 months (range, 8 to 79 months), there were no late deaths (actuarial survival at 79 months, 96.9% +/- 0.02%). Serial echocardiograms demonstrated evidence of growth of the viable tunnels. Postoperatively, there was transient depression of ejection fraction in all patients (p = 0.000). CONCLUSIONS: Supraventricular arrhythmias after extracardiac Fontan are more common in patients with heterotaxy syndrome, bilateral superior venae cavae, systemic ventricular dysfunction, and those undergoing completion Fontan operation. The viable tunnel may emerge as an optimal alternative by virtue of reduction of supraventricular arrhythmias, elimination of the need for anticoagulation, and addressing the issue of growth potential in selected patients.

Adolescent↗

PubMed2002

L-phenylalanine and NPS R-467 synergistically potentiate the function of the extracellular calcium-sensing receptor through distinct sites.

The extracellular calcium (Ca(2+)(o))-sensing receptor (CaR) can be potentiated by allosteric activators including calcimimetics and l-amino acids. In this study, we found that many mutations had differential effects on the functional modulation of the CaR by these two allosteric activators, supporting the idea that these modulators act through distinct sites. 10 mm l-phenylalanine and 1 microm NPS R-467, submaximal doses of the two agents, each elicited similar modulation of R185Q. However, there are different relative potencies for these two modulators with some receptors being more responsive to l-phenylalanine and others being more responsive to NPS R-467. The responsiveness of the CaR to Ca(2+)(o) appears to be essential to observe the potentiating action of l-phenylalanine but not of NPS R-467 on the receptor. NPS R-467 reduces the Hill coefficients of the wild-type as well as mutant receptors, suggesting that engagement of all Ca(2+) binding sites is not required when the receptor is activated by NPS R-467. In contrast, l-phenylalanine has little effect on the Hill coefficients of mutant receptors. The two-site model is further supported by the observation that these two classes of modulators exert a synergistic effect on CaRs with inactivating mutations that are responsive to both modulators.

Allosteric Regulation↗

PubMed1998

Alcohols potentiate the function of 5-HT3 receptor-channels on NCB-20 neuroblastoma cells by favouring and stabilizing the open channel state.

1. 5-HT3 receptor-mediated ion current was recorded from NCB-20 neuroblastoma cells using the whole-cell patch-clamp technique. Rapid drug superfusion was used to study the mechanism of alcohol potentiation of 5-HT3 receptor function and to analyse effects of alcohols on receptor-channel kinetics in detail. 2. Trichloroethanol (TCEt) increased in a dose-dependent way the initial slope, 20-80% rise time and measured desensitization rate of the current induced by low concentrations (1-2 microM) of 5-HT. Ethanol (EtOH) and butanol (ButOH) had similar effects on the 5-HT3 receptor-induced current. 3. TCEt and ButOH decreased the measured desensitization rate of current induced by 10 microM 5-HT, a maximally effective concentration of agonist. These alcohols also increased the relative amplitude of steady state to peak current induced by 2 or 10 microM 5-HT, indicating a possible decrease in the intrinsic rate of desensitization. 4. TCEt also decreased the deactivation rate of the current activated by 2 microM 5-HT after a short pulse of agonist application. 5. Current sweeps generated by 1 microM 5-HT in the presence or absence of 10 mM TCEt or 100 mM EtOH were well fitted using a modified standard kinetic model derived from the nicotinic acetylcholine receptor. This analysis indicated that potentiation by alcohols could be accounted for by increases in the association rate constant coupled with decreases in the dissociation and desensitization rate constants. 6. This study suggests that alcohols potentiate 5-HT3 receptor-mediated current by both increasing the rate of channel activation and stabilizing the open state by decreasing the rates of channel deactivation and desensitization.

Alcohols↗

PubMed2007

Modification and optimization of the united-residue (UNRES) potential energy function for canonical simulations. I. Temperature dependence of the effective energy function and tests of the optimization method with single training proteins.

We report the modification and parametrization of the united-residue (UNRES) force field for energy-based protein structure prediction and protein folding simulations. We tested the approach on three training proteins separately: 1E0L (beta), 1GAB (alpha), and 1E0G (alpha + beta). Heretofore, the UNRES force field had been designed and parametrized to locate native-like structures of proteins as global minima of their effective potential energy surfaces, which largely neglected the conformational entropy because decoys composed of only lowest-energy conformations were used to optimize the force field. Recently, we developed a mesoscopic dynamics procedure for UNRES and applied it with success to simulate protein folding pathways. However, the force field turned out to be largely biased toward -helical structures in canonical simulations because the conformational entropy had been neglected in the parametrization. We applied the hierarchical optimization method, developed in our earlier work, to optimize the force field; in this method, the conformational space of a training protein is divided into levels, each corresponding to a certain degree of native-likeness. The levels are ordered according to increasing native-likeness; level 0 corresponds to structures with no native-like elements, and the highest level corresponds to the fully native-like structures. The aim of optimization is to achieve the order of the free energies of levels, decreasing as their native-likeness increases. The procedure is iterative, and decoys of the training protein(s) generated with the energy function parameters of the preceding iteration are used to optimize the force field in a current iteration. We applied the multiplexing replica-exchange molecular dynamics (MREMD) method, recently implemented in UNRES, to generate decoys; with this modification, conformational entropy is taken into account. Moreover, we optimized the free-energy gaps between levels at temperatures corresponding to a predominance of folded or unfolded structures, as well as to structures at the putative folding-transition temperature, changing the sign of the gaps at the transition temperature. This enabled us to obtain force fields characterized by a single peak in the heat capacity at the transition temperature. Furthermore, we introduced temperature dependence to the UNRES force field; this is consistent with the fact that it is a free-energy and not a potential energy function. beta

Biophysics↗

PubMed2000

Structure and activity of specific inhibitors of thymidine phosphorylase to potentiate the function of antitumor 2'-deoxyribonucleosides.

A new class of 5-halogenated pyrimidine analogs substituted at the 6-position was evaluated as competitive inhibitors of thymidine phosphorylase (TPase). The most potent member of the series was 5-chloro-6-(2-iminopyrrolidin-1-yl)methyl-2,4(1H,3H)-pyrimidine dio ne hydrochloride (TPI), which has an apparent K(i) value of 1.7 x 10(-8) M. TPI selectively inhibited the activity of TPase, but not that of uridine phosphorylase, thymidine kinase, orotate phosphoribosyltransferase, or dihydropyrimidine dehydrogenase. In vitro inhibition studies of TPI using a thymidine analogue, 5-trifluoromethyl-2'-deoxyuridine (F(3)dThd), as the substrate demonstrated that F(3)dThd phosphorolytic activity was inhibited markedly by TPI (1 x 10(-6) M) in extracts from the liver, small intestine, and tumors of humans, from the liver and small intestine of cynomolgus monkeys, and from the liver of rodents, but not from the liver or small intestine of dogs or the small intestine of rodents, suggesting that the distribution of TPase differs between humans and animal species, and that TPI could contribute to the modulation of TPase in humans. When F(3)dThd or 5-iodo-2'-deoxyuridine (IdUrd) was coadministered to mice with TPI at a molar ratio of 1:1, the blood levels of F(3)dThd (or IdUrd) were about 2-fold higher than when F(3)dThd (or IdUrd) was administered alone. In monkeys, the maximum concentration (C(max)) and the area under the concentration-time curve (AUC) after oral F(3)dThd alone were 0.23 microg/mL and 0.28 microg. hr/mL, respectively, but markedly increased to 15.18 microg/mL (approximately 70-fold) and 28.47 microg. hr/mL (approximately 100-fold), respectively, when combined with equimolar TPI. Combined oral administration of TPI significantly potentiated the antitumor activity of F(3)dThd on AZ-521 human stomach cancer xenografts in nude mice. In conclusion, TPI may contribute not only to inhibition of TPase-mediated biological functions but also to potentiation of the biological activity of various 2'-deoxyuridine and thymidine derivatives by combining with them.

Administration, Oral↗

PubMed2000

[Heart failure with conserved systolic function. Therapeutic potential with beta blocking agents].

It is increasingly recognized that the syndrome of congestive heart failure may occur in the absence of any abnormality of left ventricular systolic function. In this situation, the clinical picture of heart failure, particularly the presence of symptoms and/or signs of pulmonary congestion, is usually considered a consequence of an abnormal diastolic function of the left ventricle (diastolic heart failure). However, in the individual patient, several other potential causes should be taken into account before attributing to an isolated diastolic dysfunction of the left ventricle the pathogenetic role of clinical presentation. In fact, due to the current lack of validated criteria for diagnosis of diastolic heart failure, it still represents an exclusion diagnosis in the clinical setting. Prevalence of heart failure with preserved left ventricular systolic function is widely variable among the different studies, from 13% to over 70%, with most reports showing a prevalence of 30-40%. These differences depend on several factors, such as the criteria used for diagnosis of heart failure, as well as those used for recognizing a normal systolic function or the clinical setting considered (for example hospital versus community). According to an analysis of the studies published, heart failure with preserved left ventricular systolic function seems to be more common in the female sex and in elderly patients, and it is associated with hypertension and electrocardiographic or echocardiographic evidence of left ventricular hypertrophy. Atrial fibrillation, either paroxysmal or chronic, is common and may represent a precipitating factor of clinical deterioration. According to most studies, patients with preserved left ventricular systolic function show, compared to patients with reduced left ventricular systolic function, a better prognosis, as indicated by a lower mortality and hospital readmission rates. Regarding the therapy of these patients, it is known that there are virtually no well-controlled studies of the effect of pharmacological treatment on outcome. Accordingly, the therapeutic approach of heart failure with preserved systolic function is currently based on a careful pathophysiological interpretation of clinical picture in the individual patient.

Adrenergic beta-Antagonists↗

PubMed1997

Squamate Harderian gland: an overview.

BACKGROUND: The Harderian gland is an orbital feature found in most terrestrial vertebrates. Although there have been several reports on the structure of the squamate Harderian gland, there has been little recent discussion as to its potential function. This article reviews both the recent morphological observations and their implications on the potential functions of the squamate Harderian gland. METHODS: Literature on the gross structure, histochemistry, and ultrastructure of the squamate Harderian gland and associated structures was reviewed. These observations were then used to assess morphologically the likelihood of the proposed functions. RESULTS: A high level of morphological variation was found in the squamate Harderian gland. Three functional hypotheses, including roles in orbital lubrication, digestion, and vomerolfaction, were considered. Both morphology of the squamate Harderian gland and the presence of alternate secretory sources suggest that it is unlikely to function in orbital lubrication. There is little evidence to suggest a function in digestion. Both the presence of the connecting lacrimal apparatus and the reduced intrinsic secretory capacity of the vomeronasal organ suggest that the Harderian gland may function in vomerolfaction. CONCLUSIONS: The most likely role of the squamate Harderian gland seems to be in vomerolfaction. Morphological variations observed in the Harderian gland may mirror the different degrees and mechanisms of vomerolfaction. Further studies, including comparative morphological, experimental, and microchemical analyses, are required to test this hypothesis.

Animals↗

PubMed1996

Monitoring of intra-operative visual evoked potentials during functional endoscopic sinus surgery (FESS) under general anaesthesia.

Functional endoscopic sinus surgery (FESS) is an effective treatment for inflammatory sinus disease. The potential for major complications during FESS is high particularly under general anaesthesia. The most serious of these is injury to the eye leading to blindness. We looked at the feasibility of monitoring flash visual evoked potentials (VEP) simultaneously from both eyes during FESS. Five patients were included in this preliminary study. A haptic contact lens connected by fibreoptic cable to a photostimulator was placed on the eyes and stimulus of comparable intensity to a conventional strobe was delivered. We found that an increase in P100 latency to be an indicator of optic nerve compression. However, for this to be useful the diastolic blood pressure should not fall below 50 mmHg, the oxygen saturation should be maintained at 98 per cent and bleeding should be minimized during surgery. The changes in the amplitude of P100 was not found to be useful. While there is no substitute for learning endoscopic surgery by cadaveric dissection and supervised training we believe that in selected cases VEP monitoring can be employed with profit.

Anesthesia, General↗

PubMed2004

Pronlonged hypothermic machine perfusion preserves hepatocellular function but potentiates endothelial cell dysfunction in rat livers.

BACKGROUND: Although hypothermic machine perfusion (HMP) preservation has been shown to improve organ function and to expand the organ donor pool, problems still exist with the current HMP technology for liver preservation. The present study was conducted to investigate endothelial and hepatocellular functions following extended HMP (> r =24 hr) in rat liver model. METHODS: Following 24-hour hypothermic HMP with University of Wisconsin (UW) solution or 24-hour simple cold storage (SCS), livers were reperfused with Krebs-Henseleit buffer solution at 37 degree C for 30 minutes. Hepatocyte damage and function were assessed by measuring lactate dehydrogenase (LDH) activity, bile production, and indocyanine green (ICG) extraction. Sinusoidal endothelial cell (SEC) function and permeability were determined by hyaluronic acid (HA) uptake and multiple indicator dilution (MID) method, respectively. RESULTS: After 24-hour hypothermic preservation, HMP livers showed lower released LDH levels, higher bile flow rate, and greater hepatic ICG uptake compared with SCS livers. However, LDH levels became significantly higher in HMP than in SCS after 30 minutes of warm perfusion. The increased enzyme levels were accompanied by a significant increase in endothelial permeability to albumin and a decrease in hyaluronic acid uptake in HMP compared to SCS. Liver wet/dry weight ratio confirmed a greater edema in HMP livers than SCS livers. CONCLUSION: These results suggest that 24-hour hypothermic HMP may help preservation of hepatocyte function, but endothelial cell dysfunction during the cold preservation may play a key role in hepatocyte dysfunction and parenchymal cell death upon reperfusion.

Adenosine↗

PubMed1989

Characterization of four homologous L chain variable region genes that are related to 6B6.6 idiotype positive human rheumatoid factor L chains.

A significant proportion of monoclonal IgM rheumatoid factors (RF) from patients with mixed cryoglobulinemia express a KIIIa L chain-associated cross-reactive idiotype, termed 6B6.6. Previously, we reported the isolation from a patient with a monoclonal RF of a Vk gene, termed Humkv328, whose deduced amino acid sequence differs by three and seven residues from the L chains of the 6B6.6-positive RF Les and Pom, respectively. To further delineate the genetic basis of the 6B6.6 cross-reactive idiotype, we isolated from the same patient another Vk gene, termed Humkv329, which differs from kv328 by only three bases over a stretch of 1331 nucleotides sequenced. However, kv329 has a stop codon at amino acid position 94, and is thus a pseudogene. Therefore, we screened a second genomic library from an unrelated individual and isolated two potential function Vk genes (i.e., Humkv328h2 and Humkv328h5) which are highly homologous to Humkv328. All three potential functional Vk genes differ from each other by one to six bases over a 1331-bp stretch and all encode the same Vk region amino acid sequence. Among the six bases by which Humkv328h5 differs from Humkv328, two are in the conserved pentadecanucleotide region, which is known to be important in the regulation of k L chain transcription. In the future it will be important to ascertain the potential association of polymorphisms in the conserved pentadecanucleotide region with RF associated autoimmune and lymphoproliferative diseases.

Amino Acid Sequence↗

PubMed1996

Pharmacokinetics, effects on renal function, and potentiation of atracurium-induced neuromuscular blockade after administration of a high dose of gentamicin in isoflurane-anesthetized dogs.

OBJECTIVE: To determine pharmacokinetics, renal effects, and effect on atracurium-induced neuromuscular blockade of a high dose of gentamicin in isoflurane-anesthetized dogs. ANIMALS: 6 healthy, adult, mixed-breed dogs, anesthetized twice and receiving gentamicin (6 mg/kg of body weight, i.v.) or saline solution. PROCEDURE: Blood samples were collected before and at intervals after gentamicin administration. Pharmacokinetic values were evaluated by use of multivariant stepwise linear regression analysis. Gentamicin-induced renal changes were assessed by comparing pretreatment and 12- to 24-hour posttreatment values for serum urea nitrogen, serum creatinine, urine creatinine-to-gamma-glutamyl-transferase ratio, and urinalysis. Neuromuscular blockade, maintained by atracurium infusion, was assessed, using the train-of-four response. At stable 50% depression of first twitch (T1), gentamicin or saline solution was given. Before and at posttreatment intervals for 60 minutes, T1% and fourth twitch-to-T1 ratio were recorded. The infusion was discontinued and 50 to 75% T1 recovery time was recorded. At 75% T1, edrophonium (0.5 mg/kg) was administered i.v.. RESULTS: Mean values for volume of distribution and clearance were 0.263 L/kg and 2.0 ml/min/kg, respectively. Mean maximal serum concentration of gentamicin was 46.4 micrograms/ml. Pre and posttreatment values for serum urea nitrogen, serum creatinine, urine creatinine-to-gamma-glutamyltransferase ratio, and other urine analytes were not significantly different. Mean (+/- SD) values for T1% and fourth twitch-to-T1 ratio decreased significantly after gentamicin (depression was maximal at 5 minutes). Recovery time (50 to 75% T1) was not different between groups. Edrophonium restored twitch to baseline. CONCLUSIONS: Mean values for apparent volume of distribution and total body clearance of gentamicin were similar to values in unanesthetized dogs. Mean maximal serum concentration of gentamicin was greater than that in unanesthetized dogs. Renal function was unaffected. Gentamicin potentiated atracurium-induced neuromuscular blockade, but did not affect recovery time.

Anesthesia↗

PubMed1981

Life-span alterations in visually evoked potentials and inhibitory function.

Visually evoked potentials (VEPs) elicited by patterned and unpatterned flashes were recorded from 211 healthy males aged 4-90 years. A measure of similarity between the two kinds of VEPs was obtained by correlating the digital values comprising the two waveforms. Across the life-span, correlations followed a U-shaped curve; patterned and unpatterned flash VEPs were most alike for the youngest and oldest subjects. This age effect, localized to scalp areas overlying visual cortex, is compatible with a concept of reduced inhibitory functioning within the visual systems of the young and the old. At central scalp, patterned and unpatterned flash VEP waveforms were more effectively differentiated by the right hemisphere. This observation agrees that the right hemisphere specializes in analyses of spatial material.

Adolescent↗

PubMed1997

Tsalen- and Tsalpn-Based Nickel Complexes with Two Aldehyde Functionalities as Potential Synthons for Thiophenolate-Containing Di- and Polynucleating Acyclic and Macrocyclic Ligands.

Tsalen- and tsalpn-based nickel complexes with aldehyde functionalities have been prepared (tsalen = N,N'-ethylenebis(thiosalicylideneaminato)(2-) and tsalpn = N,N'-propane-1,3-diyl(thiosalicylideneaminato)(2-)). One of the complexes has been structurally characterized: Ni(pftp) (pftp = N,N-ethylene(6-formyl-4-methyl-2-methyliminatothiophenolato)(2-)) crystallizes in the monoclinic space group C2/c with a = 28.761(7), b = 8.582(2), c = 7.841(4) Å; beta = 98.92(3) degrees, and Z = 4. Ni(pftp) and Ni(eftp) (efpt = N,N-ethylene(6-formyl-4-methyl-2-methyliminatothiophenolato)(2-)) were used as synthons for acyclic and macrocyclic complexes and a prototype of each has been structurally characterized. The Schiff base derivative of Ni(pftp) and 2-(2-aminoethyl)pyridine gives the acyclic complex, Ni(peptp) (peptp =N,N-propane-1,3-diyl(6-(N-(2-ethylpyridyl)iminomethyl)-4-methyl-2-methyliminatothiophenolato)(-)) with the two ethylpyridyl arms furnishing an "open site", which in this complex is vacant, and a "closed site", in which the Ni(2+) is located. Ni(peptp) crystallizes in the monoclinic space group P2(1)/n with a = 10.247(7), b = 21.886(8), c = 15.662(9) Å; beta = 92.58(6) degrees, and Z = 4. Schiff base condensation of Ni(pftp) with diaminopropane gave two different macrocyclic dinickel complexes [L(1)Ni(2)](ClO(4))(2) and L(2)Ni(2). L(1) and L(2) are the 2 + 2 and 4 + 4 macrocycles, respectively, comprising two propylenediamine and two thiocresol units and four propylenediamine and four thiocresol units, respectively. Crystals of L(2)Ni(2) (L(2) = (10,23,36,49-tetramethyl-13,26,39,52-tetramercapto-2,6,15,19,28,32,41,45-octaaza-1,7,14,20,27,33,40,46-octaene[7.7.7.7]metacyclophane) are of poor quality and crystallize in the C2/c space group with a = 31.517(14), b =8.980(2), c = 26.822(12) Å; beta = 117.17(2) degrees, and Z = 4.

Journal Article↗

PubMed2002

Endomorphins 1 and 2 inhibit IL-10 and IL-12 production and innate immune functions, and potentiate NF-kappaB DNA binding in THP-1 differentiated to macrophage-like cells.

We evaluated immunological effects of opioid peptides endomorphins 1 and 2 on the production of interleukin-10 (IL-10) and IL-12 cytokines, functions related to innate immunity and NF-kappaB DNA binding in human cell line THP-1. Endomorphins 1 and 2 inhibited lipopolysaccharide (LPS)-stimulated IL-10 and IL-12 production in THP-1 differentiated to macrophage-like cells by phorbol 12-myristate 13-acetate (PMA). Similarly, they suppressed LPS-stimulated IL-10 and IL-12 production in THP-1 matured to monocytes by 1alpha,25-dihydroxyvitamin D3. In addition, endomorphins 1 and 2 led to marked potentiation of NF-kappaB binding in THP-1 differentiated to macrophage-like cells. Furthermore, these endomorphins further potentiated LPS-induced NF-kappaB binding. Moreover, they inhibited chemotaxis, phagocytosis of Escherichia coli and PMA-stimulated production of hydrogen peroxide in THP-1 differentiated to macrophage-like cells. These results suggest that endomorphins 1 and 2 may inhibit THP-1 functions, such as cytokine production and functions related to innate immune, and potentiate NF-kappaB DNA binding in THP-1.

Cell Differentiation↗

PubMed2004

Pinning of fluid membranes by periodic harmonic potentials.

We analyze the thermal fluctuations of fluid membranes in the presence of periodic confining harmonic potentials. This is a simple model of the biologically important, inhomogeneous attachment of the cytoskeleton to the external, fluid membrane of the cell. We study a two-dimensional checkerboard potential as well as one-dimensional, sinusoidal and periodic highly localized, delta function potentials. The membranes are described by an energy functional that includes the curvature bending modulus of the membrane and the harmonic external potential. We predict the magnitude of the membrane shape fluctuations. The sinusoidal potentials give a spontaneous surface tension, and an emergent intermediate-range order in the membrane undulations. The delta function potentials induce a renormalization of the curvature modulus, with perfect pinning at the delta potential sites. After spatial averaging, the delta-function potentials also give rise to an effective surface tension. Finally, we compare these results with measurements of the fluctuations of the red-blood cell membrane, which shows the effects of cytoskeleton attachment to the cellular membrane.

Journal Article↗

PubMed1996

Adjusting potential energy functions for lattice models of chain molecules.

Lattice models of proteins can approximate off-lattice structure to arbitrary precision with RMS (root mean squared) deviations roughly equal to half the lattice spacing (Rykunov et al., Proteins 22:100-109, 1995; Reva et al., J. Comp. Biol., 1996). However, even small distortions in the positions of chain links lead to significant errors in lattice-based energy calculations (Reva et al., J. Comp. Chem., 1996). These errors arise mainly from rigid interactions (such as steric repulsion) which change their energies considerably at a range which is much smaller than the usual accuracy of lattice modeling (> 1.0 A). To reduce this error, we suggest a procedure of adjusting energy functions to a given lattice. The general approach is illustrated with energy calculations based on pairwise potentials by Kolinski et al. (J. Chem. Phys. 98:1-14, 1993). At all the lattice spacings, from 0.5-3.8 A, the lattice-adjusted potentials improve the accuracy of lattice-based energy calculations and increase the correlations between off-lattice and lattice energies.

Models, Chemical↗

PubMed2004

Leukaemia inhibitory factor (LIF) gene mutations in women with unexplained infertility and recurrent failure of implantation after IVF and embryo transfer.

OBJECTIVE: Leukaemia inhibitory factor (LIF) plays a central role in the control of implantation. We undertook this study to investigate the prevalence of LIF gene alterations in women with unexplained infertility and with recurrent failure of implantation after in vitro fertilisation (IVF) and embryo transfer. PATIENTS AND METHODS: Forty five women with recurrent failure of implantation after IVF (group A), 50 with unexplained infertility (group B) and 105 fertile women (controls) were screened for LIF gene mutations. Standard genomic DNA extraction, PCR amplification of the LIF gene and single-strand conformation polymorphism (SSCP) analysis were used to search for mutations which were subsequently confirmed by DNA sequencing. RESULTS: In group A, one woman was identified as having a neutral LIF gene polymorphism in exon 3 without affecting protein conformation. In group B, one woman with a heterozygous mutation and one with a neutral polymorphism were detected. In controls, only one woman with a neutral polymorphism in the intron between exons 2 and 3 was found. The woman with a potentially functional LIF gene mutation in group B achieved an ongoing clinical pregnancy after ovarian superovulation. DISCUSSION: Potentially functional mutations in the LIF gene do infrequently occur in women with unexplained infertility and may play a role in the etiology of infertility. However, routine screening for LIF mutations or polymorphisms in these women is not justified for the low prevalence of gene alterations.

Abortion, Habitual↗

PubMed2000

Parabolic plasma sheath potentials and their implications for the charge on levitated dust particles

Analysis of several numerical plasma sheath models, as well as data from several previously reported experiments, is shown to indicate that the sheath potential function may often be very closely approximated with a parabola. We also demonstrate that once this potential function is suitably determined the charge on isolated dust particles levitated in the plasma sheath may be calculated directly from their equilibrium heights.

Journal Article↗