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At least 793 records · Page 44Linked to original sources
PubMed1995

Molecular characterization of 16p deletions associated with inversion 16 defines the critical fusion for leukemogenesis.

The inversion of chromosome 16 [inv(16)] in acute myeloid leukemia (AML) is associated with a p-arm deletion in a subset of patients. The inversion results in two fusion genes: 5'-CBFB/MYH11-3' on 16p and 5'-MYH11/CBFB-3' on 16q. We have studied cells from 42 patients with inv(16) (38 patients) or t(16;16) (four patients) to define the frequency and characteristics of the deletion further. Using fluorescence in situ hybridization (FISH) with probes from cosmids, cosmid contigs, and yeast artificial chromosomes (YACs), we found that six patients with inv(16) had a deletion of between 150 and 350 kb centromeric to the p-arm inversion breakpoint cluster region (p-ibc). This region was shown to contain the 5' portion of the myosin heavy chain (MYH11) gene. YACs containing the p-ibc, which had been useful as FISH probes in the diagnosis of inv(16), detected the inversion in deletion as well as nondeletion patient cells. Thus, the deleted region identified in patients is entirely contained within the human genomic content of the YACs. Southern blot experiments using probes flanking the p-ibc indicated that the deletion removes segments within 10 kb centromeric of the p-ibc. Reverse transcription-polymerase chain reaction (RT-PCR) using primers from the 5' region of CBFB and the 3' region of MYH11 (distal to the p-ibc) produced the 5'-CBFB/MYH11-3' chimeric transcript in inv(16)/del patients. These data confirm that the 5'-CBFB/MYH11-3' chimeric transcript, rather than the reciprocal 5'-MYH11/CBFB-3', is the critical product for chromosome 16-related leukemogenesis.

Acute Disease↗
PubMed1993

Identification of yeast artificial chromosomes containing the inversion 16 p-arm breakpoint associated with acute myelomonocytic leukemia.

We report the cloning of the chromosome 16 p-arm breakpoint involved in inversion 16(p13;q22) associated with subtype of acute myelomonocytic leukemia (AMML) M4Eo. Inter-Alu polymerase chain reaction (PCR) products from a series of interspecific somatic cell hybrids that contain only small portions of the human chromosome 16 p-arm were generated for use as fluorescent in-situ hybridization (FISH) probes. When applied to patient cells, rapid and unambiguous identification of the inversion resulted. Using FISH analysis, cosmid clones associated with the hybrids were identified that bracketed the p-arm breakpoint. A repeat-free fragment of one of these cosmids (35B11) when used as probe on Southern blots from pulsed-field gels identified rearranged macrorestriction fragments in patient DNA. Yeast artificial chromosomes (YACs) were isolated using sequences derived from cosmids flanking 35B11 in a cosmid contig. Of 4 YACs so identified, 3 were shown by FISH to cross the inversion-16 p-arm breakpoint. Therefore, the breakpoint has been molecularly cloned, and identified as being within these 3 YACs. These clones will facilitate the unraveling of the genetic events associated with inversion-16 and are available tools with immediate clinical application.

Base Sequence↗
PubMed1998

[Analysis of inversion in intron 22 of the factor F VIII:C gene in patients with hemophilia A in the Slovak population].

Hemophilia A is the result of Factor F VIIIC (F8C) gene mutations. Predominating mutation is inversion, occurring in about 50% of patients with severe form of the disease. Inversion is the result of homologous recombination between gene A located on the 22. introne of the F8C gene and one of its telomeric copies located about 500 kb from 5'end of the factor F VIIIC gene. This study presents the results of this mutation screening in 84 nonrelated patients with hemophilia A. Inversion was identified in 22 (50%) of 44 patients with severe form and in 1 (from 13) with moderate form of the disease. Distal type of inversion was more frequent (82.6%) than proximal one. The identification of iversions enabled direct DNA diagnosis in 50% of patients with severe form of the disease and will be successfully used in the prenatal diagnosis and carrier testing, mainly in families with sporadic occurrence of the disease. (Tab. 1, Fig. 2, Ref. 18.)

Chromosome Inversion↗
PubMed1988

Simple ligation vs stump inversion in appendectomy.

The records of 886 patients who had appendectomy performed by the same surgeons within a five-year period were used to contrast appendiceal stump inversion vs simple ligation. Our analysis contrasted inversion vs simple ligation techniques as related to postoperative complications, hospital stay, and pathologic diagnosis. Adhesions requiring repeated operation to relieve bowel obstruction occurred in five of 87 patients with acute gangrenous appendicitis treated by inversion. Of 106 patients with acute gangrenous appendicitis treated with simple ligation, postoperative obstruction developed in none. No other statistically significant differences existed between the two techniques. These data suggest that simple ligation is at least as good as and probably better than inversion of the appendiceal stump.

Acute Disease↗
PubMedDate not supplied

The efficiency of adiabatic inversion for perfusion imaging by arterial spin labeling.

Velocity-driven adiabatic inversion is an attractive method for labeling arterial blood spins for quantitative perfusion imaging. To quantify perfusion and to optimize experimental parameters, an accurate estimate of labeling efficiency is required. We present theoretical and numerical methods to calculate the labeling efficiency over a wide range of experimental and physiologic parameters. The results are compared to experimental measurements in vivo. Inversion efficiency was found to be higher than previously assumed and relatively insensitive to flow velocity and the amplitude of the RF irradiation used for inversion. Assuming laminar flow, labeling efficiencies of greater than 90% are easily obtainable over a broad range of flow velocities. For applications where RF power deposition is a limiting factor such as at high field strengths, labeling efficiency can be maintained by reducing the labeling gradient. These results further illustrate the capability of adiabatic inversion to effectively label flowing blood.

Adult↗
PubMed1997

Bi-directional chiral inversion of ketoprofen in CD-1 mice.

The R enantiomers of some of the 2-arylpropionic acid non-steroidal antiinflammatory drugs (NSAIDs) are known to undergo metabolic chiral inversion to their more pharmacologically active antipodes. This process is drug and species dependent and usually unidirectional. The S to R chiral inversion, on the other hand, is rare and has been observed, in substantial extents, only for ibuprofen in guinea pigs and 2-phenylpropionic acid in dogs. After i.p. administration of single doses of racemic ketoprofen or its optically pure enantiomers to male CD-1 mice and subsequent study of the concentration time-course of the enantiomers, we noticed substantial chiral inversion in both directions. Following racemic doses, no stereoselectivity in the plasma-concentration time courses was observed. After dosing with optically pure enantiomer, the concentration of the administered enantiomer predominated during the absorption phase. During the terminal elimination phase, however, the enantiomers had the same concentrations. Our observation is suggestive of a rapid and reversible chiral inversion for ketoprofen enantiomers in mice.

Animals↗
PubMed1999

Ring inversion barrier of diazepam and derivatives: An ab initio study.

Systematic ab initio calculations were performed to investigate the ring inversion process of various 1,4-diazepines including diazepam, N(1)-desmethyldiazepam, and 3-methyl-N(1)-desmethyldiazepam. The diazepine ring adopts a shape of a boat; owing to asymmetric substitution two such boats are possible in mirror image relation to each other. In the present study both structural and solvent effects were investigated on the energetics of ring inversion of nine diazepine derivatives. The calculated ring inversion barriers for diazepam (17.6 kcal/mol) and N(1)-desmethyldiazepam (10.9 kcal/mol) are in good agreement with the corresponding experimental data. In the cases of diazepam and N(1)-desmethyldiazepam, the calculated minimum energy path of the ring inversion is asymmetric contrary to the fact that the terminals (M and P conformers) are equienergetic.

Diazepam↗
PubMed1999

Multislice perfusion imaging in human brain using the C-FOCI inversion pulse: comparison with hyperbolic secant.

Perfusion studies based on pulsed arterial spin labeling have primarily applied hyperbolic secant (HS) pulses for spin inversion. To optimize perfusion sensitivity, it is highly desirable to implement the HS pulse with the same slice width as the width of the imaging pulse. Unfortunately, this approach causes interactions between the slice profiles and manifests as residual signal from static tissue in the resultant perfusion image. This problem is currently overcome by increasing the selective HS width relative to the imaging slice width. However, this solution increases the time for the labeled blood to reach the imaging slice (transit time), causing loss of perfusion sensitivity as a result of T(1) relaxation effects. In this study, we demonstrate that the preceding problems can be largely overcome by use of the C-shaped frequency offset corrected inversion (FOCI) pulse [Ordidge et al., Magn Reson Med 1996;36:562]. The implementation of this pulse for multislice perfusion imaging on the cerebrum is presented, showing substantial improvement in slice definition in vivo compared with the HS pulse. The sharper FOCI profile is shown to reduce the physical gap (or "safety margin") between the inversion and imaging slabs, resulting in a significant increase in perfusion signal without residual contamination from static tissue. The mean +/- SE (n = 6) gray matter perfusion-weighted signal (DeltaM/M(o)) without the application of vascular signal suppression gradients were 1.19 +/- 0. 10% (HS-flow-sensitive alternating inversion recovery [FAIR]), and 1. 51 +/- 0.11% for the FOCI-FAIR sequence. The corresponding values with vascular signal suppression were 0.64 +/- 0.14%, and 0.91 +/- 0. 08% using the HS- and FOCI-FAIR sequences, respectively. Compared with the HS-based data, the FOCI-FAIR results correspond to an average increase in perfusion signal of up to between 26%-30%. Magn Reson Med 42:1098-1105, 1999.

Brain↗
PubMed1994

FISH mapping of a human chromosome 16 constitutional pericentric inversion inv(16)(p13q22) found in a large kindred.

Fluorescence in situ hybridization analysis (FISH) was used to map the constitutional chromosome 16 pericentric inversion breakpoints inv(16)(p13q22) detected in one individual (II-2) from a large kindred [Bianchi et al., 1992: Am J Med Genet 43:791-795]. The breakpoints found in individual II-2 mapped to distinctly different locations than the chromosome 16 pericentric inversion breakpoints commonly acquired in acute nonlymphocytic leukemia. The constitutional pericentric inversion breakpoints also do not map to regions where low abundance repetitive DNA sequences found in bands 16p13 and q22 are located. The results indicate that low abundance, chromosome 16-specific repetitive DNA sequences in bands p13 and q22 are probably not causally related to the inversion that is found in many members of a large kindred [Bianchi et al., 1992].

Adult↗
PubMed2005

An inverse substrate orientation for the regioselective acylation of 3',5'-diaminonucleosides catalyzed by Candida antarctica lipase B?

Candida antarctica lipase B (CAL-B) catalyzes the regioselective acylation of natural thymidine with oxime esters and also the regioselective acylation of an analogue, 3',5'-diamino-3',5'-dideoxythymidine with nonactivated esters. In both cases, acylation favors the less hindered 5'-position over the 3'-position by upto 80-fold. Computer modeling of phosphonate transition-state analogues for the acylation of thymidine suggests that CAL-B favors acylation of the 5'-position because this orientation allows the thymine ring to bind in a hydrophobic pocket and forms stronger key hydrogen bonds than acylation of the 3'-position. On the other hand, computer modeling of phosphonamidate analogues of the transition states for acylation of either the 3'- or 5'-amino groups in 3',5'-diamino-3',5'-dideoxythymidine shows similar orientations and hydrogen bonds and, thus, does not explain the high regioselectivity. However, computer modeling of inverse structures, in which the acyl chain binds in the nucleophile pocket and vice versa, does rationalize the observed regioselectivity. The inverse structures fit the 5'-, but not the 3'-intermediate thymine ring, into the hydrophobic pocket, and form a weak new hydrogen bond between the O-2 carbonyl atom of the thymine and the nucleophile amine only for the 5'-intermediate. A water molecule might transfer a proton from the ammonium group to the active-site histidine. As a test of this inverse orientation, we compared the acylation of thymidine and 3',5'-diamino-3',5'-dideoxythymidine with butyryl acyl donors and with isosteric methoxyacetyl acyl donors. Both acyl donors reacted at equal rates with thymidine, but the methoxyacetyl acyl donor reacted four times faster than the butyryl acyl donor with 3',5'-diamino-3',5'-dideoxythymidine. This faster rate is consistent with an inverse orientation for 3',5'-diamino-3',5'-dideoxythymidine, in which the ether oxygen atom of the methoxyacetyl group can form a similar hydrogen bond to the nucleophilic amine. This combination of modeling and experiments suggests that such lipase-catalyzed reactions of apparently close substrate analogues like alcohols and amines might follow different pathways.

Acylation↗
PubMed1994

Evidence of absorption rate dependency of ibuprofen inversion in the rat.

Ibuprofen (IB) is a chiral 2-arylpropionic acid derivative used as a nonsteroidal antiinflammatory drug (NSAID). It undergoes substantial R to S chiral inversion in humans and rats. In addition to systemic inversion, presystemic chiral inversion has been suggested for IB in humans but only after administration of formulations with slow absorption rates. In search for a suitable animal model, the absorption rate dependency of the extent of inversion was examined in male Sprague-Dawley rats given 20 mg/kg of racemic IB in aqueous solution (Tmax, 0.6 h), suspension (Tmax, 1 h) or as sustained release granules (Tmax, 2.3 h). In addition, (R)-IB (5 mg/liter) was incubated in the presence of everted rat gut segments in an organ bath at 37 degrees. After sustained release granules, the S:R AUC ratios (7.3 +/- 1.5) were significantly higher than suspension (3.6 +/- 1.1) and solution (3.5 +/- 0.2). Accordingly, AUCS and AUCR, as percent of the total AUC (S+R), significantly increased and decreased, respectively, after administration of the sustained released granules as compared with the solution and suspension. A significant positive linear correlation was found between the S:R AUC ratios and the corresponding Tmax for (R)-IB (r = 0.82). In vitro, (R)-IB was inverted by everted jejunum (12.2 +/- 1.6%), ileum (14.2 +/- 2.0%), and colon (4.4 +/- 0.6%) segments. IB was also glucuronidated in the presence of the intestinal segments. Therefore, similar to earlier observations made in humans, in the rat, the S:R AUC ratio was positively and significantly correlated with the absorption rate from the dosage form.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Stereospecific determination, chiral inversion in vitro and pharmacokinetics in humans of the enantiomers of thalidomide.

The purposes of this work were (1) to develop a high performance liquid chromatographic (HPLC) assay for the enantiomers of thalidomide in blood, (2) to study their inversion and degradation in human blood, and (3) to study the pharmacokinetics of (+)-(R)- and (-)-(S)-thalidomide after oral administration of the separate enantiomers or of the racemate to healthy male volunteers. The enantiomers of thalidomide were determined by direct resolution on a tribenzoyl cellulose column. Mean rate constants of chiral inversion of (+)-(R)-thalidomide and (-)-(S)-thalidomide in blood at 37 degrees C were 0.30 and 0.31 h-1, respectively. Rate constants of degradation were 0.17 and 0.18 h-1. There was rapid interconversion in vivo in humans, the (+)-(R)-enantiomer predominating at equilibrium. The pharmacokinetics of (+)-(R)- and (-)-(S)-thalidomide could be characterized by means of two one-compartment models connected by rate constants for chiral inversion. Mean rate constants for in vivo inversion were 0.17 h-1 (R to S) and 0.12 h-1 (S to R) and for elimination 0.079 h-1 (R) and 0.24 h-1 (S), i.e., a considerably faster rate of elimination of the (-)-(S)-enantiomer. Putative differences in therapeutic or adverse effects between (+)-(R)- and (-)-(S)-thalidomide would to a large extent be abolished by rapid interconversion in vivo.

Adult↗
PubMed1982

A site-specific, conservative recombination system carried by bacteriophage P1. Mapping the recombinase gene cin and the cross-over sites cix for the inversion of the C segment.

The bacteriophage P1 genome carries an invertible C segment consisting of 3-kb unique sequences flanked by 0.6-kb inverted repeats. With insertion and deletion mutants of P1 derivatives the site-specific recombinase gene cin for C inversion) has been mapped adjacent to the C segment and the cix sites (for C inversion cross-over) have been located at the outside ends of the inverted repeats. Inversion of the C segment functions as a biological switch and controls expression of the gene(s) responsible for phage infectivity carried on the C segment. The cin gene product can promote recombination between a 'quasi- cix ' site on plasmid pBR322 and a cix site on P1 DNA. The junctions formed on the resulting co-integrate can also serve as cix sites. This observation implies a potential evolutionary process to bring genes under the control of a biological switch acting by DNA inversion.

Base Sequence↗
PubMed1984

Gin-mediated site-specific recombination in bacteriophage Mu DNA: overproduction of the protein and inversion in vitro.

Inversion of the G segment in bacteriophage Mu DNA occurs by a site-specific recombination event and determines the host specificity of Mu phage particles produced. Inversion is mediated by a Mu function (Gin). The gin gene has been placed under control of the inducible lambda pL promoter and a synthetic Shine-Dalgarno linker upstream of the initiation codon. The Gin protein content in induced cells is boosted to 10% of total protein. Partially purified extracts from overproducing strains promote efficient inversion of the G DNA segment in vitro which is visualized by agarose gel electrophoresis of the substrate DNA after cutting with appropriate restriction endonucleases. The in vitro reaction requires Mg, a super-coiled DNA substrate and occurs in the absence of exogenous ATP. Inversion from the G(+) to the G(-) orientation is as efficient as the switch from G(-) to G(+).

Journal Article↗
PubMedDate not supplied

Ultrastructural biologic effects of sonography with pulse inversion and microbubble contrast in rabbit liver.

PURPOSE: This prospective study was conducted to evaluate the biologic effects of microbubble destruction with pulse-inversion harmonic imaging on rabbit liver parenchyma. METHODS: The livers of 6 albino rabbits were examined sonographically by a single investigator. Three rabbits underwent contrast-enhanced sonography, with scanning starting 5 seconds after injection by using pulse-inversion harmonic imaging with a mechanical index of 1.2. Four time-triggered images were recorded at a rate of 1 frame every 2 seconds. For comparison, 3 control rabbits had pulse-inversion harmonic imaging with a mechanical index of 1.2 only, without contrast medium. Immediately after sonography, the animals were killed and uninterrupted, thin serial sections of the liver from both groups were analyzed by energy-filtered transmission electron microscopy. RESULTS: The hepatic parenchyma of rabbits exposed to contrast agents had ultrastructural damage: mitochondria with fragmented crests; interrupted rough endoplasmic reticulum; enlarged intercellular spaces; highly vacuolized cytoplasmic areas; dilated sinusoids, sometimes with an irregular and interrupted endothelial wall; fragmented hepatocyte microvilli in dilated spaces of Disse; fragmented or missing microvilli in bile canaliculi; vacuolated and lysosome-deprived hepatic cytoplasm around the bile canaliculi; markedly injured or fragmented endothelium in larger vessels; and damaged basal membrane. Control-group results indicated that exposure to ultrasound alone did not cause ultrastructural damage to hepatic cells. CONCLUSIONS: Simultaneous exposure to contrast administration and pulse-inversion harmonic imaging with a high mechanical index causes ultrastructural damage in the rabbit liver.

Animals↗
PubMed2004

Effective blood signal suppression using double inversion-recovery and slice reordering for multislice fast spin-echo MRI and its application in simultaneous proton density and T2 weighted imaging.

PURPOSE: To design a multislice double inversion-recovery fast spin-echo (FSE) sequence, with k-space reordered by inversion time at slice position (KRISP) technique, to produce black-blood vessel wall magnetic resonance imaging (MRI). MATERIALS AND METHODS: In this sequence, central k-space sampling for each slice is required at inversion time (TI) of the blood signal. To fill the entire k-space, the peripheral lines are obtained less or greater the TI and using a rotating slice order. Blood flow signal suppression was first evaluated using a phantom. Simulation studies were used to investigate FSE image quality. The final sequence was then applied to the rabbit abdominal aorta MRI at 4.7 T. RESULTS: In the flow phantom study, artifacts from slow-flowing water were substantially reduced by the KRISP technique; residual water spins were dephased by the strong phase-encoding gradient required for peripheral k-space. These dephased spins flowed into the slice plane where the center of k-space was being acquired at the TI of the flowing water signal. Multislice black-blood MR images were successfully obtained in the rabbit abdomen using the sequence with the k-trajectory optimized by the simulation study. CONCLUSION: The KRISP technique was effective both in multislice double inversion-recovery FSE and in blood signal suppression.

Abdomen↗
PubMed1995

Accuracy of numerical inversion of Laplace transforms for pharmacokinetic parameter estimation.

Numerical inversion of the Laplace transform is a useful technique for pharmacokinetic modeling and parameter estimation when the model equations can be solved in the Laplace domain but the solutions cannot be inverted back to the time domain. The accuracy of numerical inversion of the Laplace transform using an infinite series approximation due to Hosono was systematically studied by reference to 17 widely differing functions having known inverse transforms. The error of inversion was found to be very sensitive to the details of the computer implementation of the method; for example, double-precision artihmetic is essential. The method used to sum the series in the least-squares program Multi(Filt) was often unable to achieve a relative error of less than 10(-4), and a Monte Carlo simulation showed that this method is insufficiently accurate for reliable least-squares parameter estimation. Improvements to the algorithm are described whereby a better method of applying Euler's transformation is used and the number of terms summed is determined automatically by the rate of convergence of the series. The improved algorithm is more efficient in inverting easy functions and more reliable in inverting difficult functions, especially those involving a time lag. With its use, pharmacokinetic parameter estimation can be performed with essentially the same accuracy as when the function is defined in the time domain.

Algorithms↗
PubMed2002

Multislice double inversion pulse sequence for efficient black-blood MRI.

Over the last several years there has been a rapidly growing interest in high-resolution MRI of the vascular wall to assess the extent of atherosclerotic lesions. Vessels of particular clinical relevance are the carotid and coronary arteries. Currently, the preferred imaging sequence for these studies is a "black-blood" technique based on the double-inversion scheme to null the blood signal. A critical drawback of the black-blood technique, however, has been its single-slice nature, as there is only one point in time during the recovery of the blood magnetization from inversion at which the signal is completely nulled. Consequently, the total scan time can become prohibitively long, particularly when an imaging protocol includes several series of these datasets. In this work, a multiple-slice double-inversion technique is described that can reduce the scan time by a factor of two or more. It is demonstrated in vivo with examples from carotid and coronary arteries that one can acquire multiple slices with sufficient nulling of blood, following a single set of inversion pulses.

Adult↗