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PubMed1985

Vagotonic effect of inversion therapy upon resting neuromuscular tension.

Inversion therapy has become a popular treatment for low back pain but little experimental evidence is available to suggest a physiological basis for such use. On the basis of earlier work showing a vagotonic influence of inversion upon the cardiovascular system, it was our purpose to test the hypothesis that such vagotonic effects are also operative in the nervous system and thus cause decreased electrical activation of the resting musculature. To test this hypothesis 12 healthy subjects, seven female, five male (age 19-37, M = 28.9 +/- 5.8 years) were selected from among 45 who were screened on the basis of having resting IEMG scores at least one S.E. above electrical silence. Each subject acted as his own control and visited the laboratory on four occasions of which two involved EMG testing pre and post inversion for two minutes and the other two were control before and after an equivalent period of rest. The mean reduction in neuromuscular tension after inversion was 28.3 percent compared with 7.1 percent after control. This difference was significant at P less than 0.04. A two minute period appears to be sufficient and the effect may persist for as much as two hours. Heart rate and blood pressures taken before and after inversion were not significantly different from controls.

Adult↗
PubMed1993

Comparison of measured and computed epicardial potentials from a patient-specific inverse model.

This study reports the first direct comparison of measured and computed epicardial potentials in which the specific anatomy of a test subject has been used to calculate the inverse electrocardiographic model. It is now feasible to obtain low-noise body surface potential maps and to incorporate accurate anatomic data into inverse procedures for the purpose of computing epicardial potential distributions. The direct verification of computed human epicardial distributions remains an important goal. The experiment reported here obtained direct measurements from six transcutaneous pacing wires that were attached to points on the epicardial surface of the human heart in an intact subject. From the same subject, a magnetic resonance scan was used to produce a specific thoracic model consisting of 5-mm cubes. The forward model uses the finite difference method to compute a forward transfer matrix that relates each of 26 epicardial regions to body surface measurements. The inverse computation was performed by zero-order Tikhonov regularization. Body surface potentials were used in the inverse procedure to compute epicardial potentials, which were then compared with direct epicardial measurements. The computed epicardial potentials were compared to the measured ones by correlation, which gave an amplitude-independent measure of similarity. Amplitude differences and time delays in computed potentials were observed, but the morphologic trend was generally well recovered. The results obtained indicate the sensitivity of the inverse model to a number of factors. The robustness of computed epicardial distributions to errors in assumed lung conductivity is shown. Results from a nonpatient-specific, but realistic, torso model are presented.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Pacing, Artificial↗
PubMedDate not supplied

Inversion of optical configuration of alpha-methylfluorene-2-acetic acid (cicloprofen) in rats and monkeys.

A simple and sensitive radiometric method to determine the individual enantiomers of cicloprofen has been developed. 14C-Cicloprofen was converted to its L-leucine diastereoisomers, which were separated by thin-layer chromatography and quantified by measuring the radioactivity in the area corresponding to each individual diastereoisomer. This technique has also been used to measure the enantiomers of unlabeled cicloprofen by condensing with 14C-labeled L-leucine. By using the radiometric method, a unique biotransformation process, the inversion of the (-)-enantiomer of alpha-methylfluorene-2-acetic acid to its (+)-enantiomer, has been demonstrated in the rat and monkey. The rate of (-)- to (+)-inversion was found to be faster in the rat than in the monkey. After single or repeated oral adminstration of the racemic modification or the (-)-enantiomer of cicloprofen to both species, the ratio of (+)- to (-)-enantiomers of cicloprofen in plasma, urine, or bile increased with time. At 5, 22, and 48 hr after oral administration of a single 50-mg/kg dose of the (-)-enantiomer, 14C-cicloprofen in rat plasma contained 20, 50, and 79%, respectively, of the (+)-enantiomer. After receiving the same dose of (-)-enantiomer, monkey plasma contained 16.5% and 32% of (+)-enantiomer at 8 and 24 hr, respectively. After oral administration of a single 50-mg/kg dose of the (+)-enantiomer of 14C-cicloprofen to rats and monkeys, the percentage of (-)-enantiomer in plasma varied from 2 to 15%. Since the administered (+)-enantiomer contained 4% of (-)-enantiomer and the (+)-enantiomer was excreted at a faster rate than its (-)-antipode by rats or monkeys, it is not known whether an occasional small percentage increase of (-)-enantiomer in plasma resulted from the (+)-to-(-) inversion, or from faster elimination of the (+)-enantiomer. Nevertheless, if (+)-to-(-) inversion does occur in these two species, the rate is much slower than for the (-)-to-(+) inversion.

Animals↗
PubMed1993

Metabolic chiral inversion of 2-arylpropionates in different tumor cell lines.

The study presented aimed at investigating whether tumor cell lines in continuous culture could be used as in vitro model for inversion experiments. The effect of culture conditions on the extent of inversion was examined. Under optimized culture conditions human and rat tumor cell lines were incubated with the enantiomers of ibuprofen, ketoprofen and flurbiprofen, respectively. Similarly to the situation in man in vivo, inversion of R-ibuprofen occurred in human hepatoma cells, where no inversion of R-ketoprofen or negligible inversion of R-flurbiprofen could be observed. In contrast to R-flurbiprofen the R-enantiomers of ibuprofen and ketoprofen were substantially inverted in the rat hepatoma cells in accordance with observations in the rat in vivo.

Animals↗
PubMed1996

Contribution of dieting to the inverse association between energy intake and body mass index.

OBJECTIVE: To examine the association of energy and % energy from fat with body mass index (BMI) and determine if self-reported dieting altered observed associations. DESIGN: Dietary intake data based on dietary recalls from four nonconsecutive days over a 1 year period were examined relative to BMI. The relation between energy intake and % energy from fat and BMI was examined by linear regression analysis. SUBJECTS: The sample included 1854 free-living women aged 19-50 years who participated in the 1985-6 Continuing Surveys of Food Intakes by Individuals conducted by the United States Department of Agriculture. RESULTS: Reported energy intake was inversely associated with BMI (regression coefficient (beta) = -0.001 24, standard error (s.e.) = 0.000 31). Controlling for low energy dieting alone reduced the inverse energy intake-BMI association by approximately 20% (beta = -0.001 00, s.e. = 0.000 31), compared to reductions of 16%, 13% and 10%, respectively, when health status, age and education were added individually to the energy intake-BMI linear regression. Physical activity, smoking status, % energy from fat and report of low fat dieting did not reduce the energy intake-BMI association. Controlling for nondietary factors related to BMI and potentially influencing energy intake reduced the inverse energy intake-BMI association by approximately 22% (beta = -0.000 97, s.e. = 0.00025). Further adjustment for low energy dieting on day 1 reduced the inverse energy intake-BMI association by 40% (beta = -0.000 74, s.e. = 0.000 26), suggesting that intermittent energy restriction was a significant factor in the reduced energy intake reported among overweight women. Percent energy from fat was not associated with BMI (beta = 0.049, s.e. = 0.025, P = 0.055). Exclusion of 37 women reporting poor health status further attenuated the inverse association between energy intake and BMI (beta = -0.000 64), s.e. = 0.000 26), while it strengthened the previously non-significant positive association between % energy from fat and BMI (beta = 0.062; s.e. = 0.024). CONCLUSION: Intermittent energy restriction appeared to be a significant factor in the reduced energy intake reported among overweight women in this sample. Adequate assessment of energy expenditure is required to correctly interpret the association of energy intake to body weight.

Adult↗
PubMed1996

Model study of influence of extracardial factors on the inverse localization of preexcitation sites.

Inverse solution techniques are expected to help in noninvasive localization of ventricular preexcitation sites. The influence of selected extracardial factors on the accuracy of the inverse localization of the initial activation sites was studied on a model. Each of 8 simulated activation sequences was initiated in a different single starting point at the atrioventricular ring. Corresponding ecg potentials on the surface of a realistic model of inhomogeneous torso were used for the inverse localization procedure. A multiple dipole (MD) model of the cardiac generator composed of 39 segmental dipoles was used in the inverse computations. As it was shown in a previous study, the method was able to localize the 8 starting points even if a simplified torso model and a limited number of leads was used. In this study, influence of another two factors was evaluated: inaccuracy of location of the MD generator and presence of noise in surface potentials. Several shifts and rotations of the heart generator relative to its exact position were modeled. When the mean deviation of starting points was about 1 cm the mean localization error varied from 0.5 cm up to 1.0 cm for complete model data--198 surface potentials and a torso model including lungs and ventricular cavities. When a noise with uniform and Gaussian distribution was added to the surface potentials, the use of averaged body surface potentials significantly improved accuracy and stability of the inverse solution. For root mean square value of noise sigma = 14 microV the mean error of localization was 0.9 cm. For higher noise (sigma = 30 microV) the results were substantially deteriorated. The influence of a noise was studied on complete model data. (Tab. 3, Fig. 5. Ref. 6.)

Body Surface Potential Mapping↗
PubMed1997

Inversion polymorphism in laboratory strains and natural samples of Drosophila sturtevanti (saltans group, sturtevanti subgroup).

Drosophilla sturtevanti (37 strains) showed eighteen inversions, five new and thirteen previously described. Among these strains, 24 were maintained for seven to 21 years under laboratory conditions, eight for less than 1 year, and six were natural samples analysed in the first generation after collection. Flies from natural samples were the most polymorphic in the number of different inversions as well as in the frequency of flies bearing heterozygous inversions. In all cases, chromosome III presented the greatest number of inversions, and most of them occurred in strains from the Amazonian region. The data obtained were consistent with the hypothesis that the inversion variability of a species is proportional to the variability of its habitats.

Animals↗
PubMed1997

Fast inversion-recovery MR: the effect of hybrid RARE readout on the null points of fat and cerebrospinal fluid.

PURPOSE: To evaluate the effect of the hybrid RARE (rapid acquisition with relaxation enhancement) readout, commonly coupled to inversion-recovery pulse sequences, on the null inversiton time (TI) of fluid and fat using both phantoms and human volunteers. METHODS: Two phantoms, simulating fat (phantom A) and cerebrospinal fluid (phantom B), respectively, were imaged using a fast inversion-recovery sequence that coupled an inversion-recovery preparation pulse to a hybrid RARE readout. At repetition times (TRs) ranging from 700 to 20,000, the TI necessary to null the signal from each phantom (null TI) was determined for an echo train length of 4, 6, 8, 10, 12, 14, 16, 18, and 20, respectively. Plots of null TI versus echo train length at different TRs were generated for both phantoms. Fast inversion-recovery MR imaging of the cervical spine and brain was performed in healthy volunteers. At a fixed TR and TI, the adequacy of signal suppression from bone marrow and cerebrospinal fluid was assessed as a function of echo train length. RESULTS: There was a gradual decrease of null TI for both phantoms with echo train length. This decrease persisted at longer TRs for phantom B (T1 = 3175 +/- 70 milliseconds) than for phantom A (T1 = 218 +/- 5 milliseconds). In the human volunteers, there was a gradual loss of suppression of signal from bone marrow and cerebrospinal fluid, with changes in the hybrid RARE readout. CONCLUSION: To optimize specific tissue suppression, radiologists implementing fast inversion-recovery MR imaging should be aware of the effects of the hybrid RARE readout on null TI.

Adipose Tissue↗
PubMed1997

Inverse agonism at adrenergic and opioid receptors: studies with wild type and constitutively active mutant receptors.

Ligands which display inverse agonism at G protein-coupled receptors do so by decreasing the intrinsic ability of a receptor to active the cellular G protein population in the absence of an agonist ligand. Expression of the murine delta opioid receptor in Rat-1 fibroblasts resulted in the inverse agonist ICI174864 being able to cause inhibition of basal high affinity GTPase activity and of the binding of [35S]GTP gamma S in membranes of a clone (D2) of these cells which expresses high levels of the receptor. These effects were blocked by co-addition of the neutral antagonist TIPP[psi], demonstrating a requirement for the delta opioid receptor, and by pertussis toxin pretreatment of the cells, showing them to be produced via a Gi-like G protein. The inverse agonist properties of ICI174864 could also be demonstrated in whole cells. Stimulation of forskolin-amplified adenylyl cyclase activity was produced by ICI174864 following [3H]adenine prelabelling of the cells. Constitutively activated mutants of receptors should provide a convenient means to detect inverse agonists. Incubation of cells either transiently or stably transfected with a constitutively activated mutant of the human beta 2-adrenoceptor with the beta 2-inverse agonists betaxolol or sotalol, which are both able to inhibit CAM beta 2-adrenoceptor-mediated basal adenylyl cyclase activity, resulted in a strong upregulation of levels of the receptor. In the stable cells lines this effect was prevented by co-incubation with neutral antagonists but could not be reproduced by an adenylyl cyclase P-site ligand which also inhibited basal adenylyl cyclase levels.

Adrenergic beta-Antagonists↗
PubMed1992

DNA inversions in phages and bacteria.

In certain phages and bacteria, there is a recombination system that specifically promotes the inversion of a DNA fragment. These inversion events appear to act as genetic switches allowing the alternate expression of different sets of genes which in general code for surface proteins. The mechanism of inversion in one class of inversion systems (Gin/Hin) has been studied in detail. It involves the formation of a highly specific nucleoprotein complex in which not only the two recombination sites and the DNA invertase participate but also a recombinational enhancer to which the DNA-bending protein Fis is bound.

Bacteria↗
PubMed1998

In vivo identification of intermediate stages of the DNA inversion reaction catalyzed by the Salmonella Hin recombinase.

The Hin recombinase catalyzes a site-specific recombination reaction that results in the reversible inversion of a 1-kbp segment of the Salmonella chromosome. The DNA inversion reaction catalyzed by the Salmonella Hin recombinase is a dynamic process proceeding through many intermediate stages, requiring multiple DNA sites and the Fis accessory protein. Biochemical analysis of this reaction has identified intermediate steps in the inversion reaction but has not yet revealed the process by which transition from one step to another occurs. Because transition from one reaction step to another proceeds through interactions between specific amino acids, and between amino acids and DNA bases, it is possible to study these transitions through mutational analysis of the proteins involved. We isolated a large number of mutants in the Hin recombinase that failed to carry out the DNA exchange reaction. We generated genetic tools that allowed the assignment of these mutants to specific transition steps in the recombination reaction. This genetic analysis, combined with further biochemical analysis, allowed us to define contributions by specific amino acids to individual steps in the DNA inversion reaction. Evidence is also presented in support of a model that Fis protein enhances the binding of Hin to the hixR recombination site. These studies identified regions within the Hin recombinase involved in specific transition steps of the reaction and provided new insights into the molecular details of the reaction mechanism.

Alleles↗
PubMed1993

Xis and Fis proteins prevent site-specific DNA inversion in lysogens of phage HK022.

HK022, a temperate coliphage related to lambda, forms lysogens by inserting its DNA into the bacterial chromosome through site-specific recombination. The Escherichia coli Fis and phage Xis proteins promote excision of HK022 DNA from the bacterial chromosome. These two proteins also act during lysogenization to prevent a prophage rearrangement: lysogens formed in the absence of either Fis or Xis frequently carried a prophage that had suffered a site-specific internal DNA inversion. The inversion is a product of recombination between the phage attachment site and a secondary attachment site located within the HK022 left operon. In the absence of both Fis and Xis, the majority of lysogens carried a prophage with an inversion. Inversion occurs during lysogenization at about the same time as prophage insertion but is rare during lytic phage growth. Phages carrying the inverted segment are viable but have a defect in lysogenization, and we therefore suggest that prevention of this rearrangement is an important biological role of Xis and Fis for HK022. Although Fis and Xis are known to promote excision of lambda prophage, they had no detectable effect on lambda recombination at secondary attachment sites. HK022 cIts lysogens that were blocked in excisive recombination because of mutation in fis or xis typically produced high yields of phage after thermal induction, regardless of whether they carried an inverted prophage. The usual requirement for prophage excision was bypassed in these lysogens because they carried two or more prophages inserted in tandem at the bacterial attachment site; in such lysogens, viable phage particles can be formed by in situ packaging of unexcised chromosomes.

Bacterial Proteins↗
PubMed1997

Paracentric inversion involving the long arm of chromosome 9 resulting in deletion of abl gene.

We report on a new chromosomal finding in a newborn male with hypertelorism, apparently low-set malformed ears with patent canal, micrognathia with narrow high-arched palate, bilateral webbing of neck with low posterior hairline, widely spaced nipples, and complex heart anomalies. Initially, what appeared to be a simple paracentric inversion of the long arm of chromosome 9, that is, 46,XY, inv(9)(q31q34) by routine GTG-banding technique was later determined to be a paracentric inversion with deletion of the band 9q34.1 by FISH technique using an abl unique sequence DNA probe. Thus the cytogenetic diagnosis was modified to 46,XY,der(9) inv(9)(q31q34.1)del(q34.1). Nevertheless, the presence of telomeric repeat sequences in the inverted chromosome 9 suggests that either healing has occurred by adding [TTAGGG]n sequences to the non-telomeric end (q31) by the enzyme telomerase or telomeric sequences were not affected during this inversion process. This abnormality is a rare occurrence and has never been reported before either because of a high rate of lethality or it has been undetected by routine cytogenetic techniques. The other abnormal cases with apparent paracentric inversions could also have a complex nature with congenital anomalies associated with loss of "few" DNA sequences as exemplified here.

Abnormalities, Multiple↗
PubMed2001

Loss of subtelomeric sequence associated with a terminal inversion duplication of the short arm of chromosome 4.

We report on a 4(1/2)-year-old girl, who presented with multiple minor anomalies consistent with trisomy for 4p. GTG-banding identified a de novo terminal inversion duplication of distal 4p, dup(4)(p16.3p15.3). Fluorescence in situ hybridization (FISH) with a wcp4 probe confirmed the chromosome 4 origin of the additional material. FISH with a 4p subtelomere probe, D4F26, showed no signal on the dup(4) chromosome identifying a deletion of this region. Molecular analysis of 4p STS loci confirmed the subtelomeric deletion and showed loss of the paternal allele in this region. The paternal origin of the deleted region and homozygosity for one of the two paternal alleles within the region of the duplication suggests that a sister chromatid rearrangement on the paternal chromosome 4 was involved in the formation of the dup(4) chromosome. To date, the best characterized mechanisms of formation of chromosome duplications are terminal inversion duplications of 8p, which were shown to be derived from rearrangements at maternal meiosis-I. Our data show that mechanisms other than a maternal meiosis-I rearrangement can lead to the formation of terminal inversion duplications. FISH analysis with the appropriate subtelomeric probes is warranted in terminal inversion duplications to check for associated deletions.

Child, Preschool↗
PubMed2002

Recombinant 4 syndrome due to an unbalanced pericentric inversion of chromosome 4.

An informative patient with a MCA/MR syndrome consisting of developmental delay, prenatal onset growth delay, microcephaly, distinctive face, iris coloboma, and a congenital heart defect was found, on chromosome analysis, to have the following complement: 46,XY,rec(4) dup(4p) inv(4)(p14q35.1) mat. He has a partial 4p trisomy/distal 4q deletion due to an unbalanced pericentric inversion inherited from his mother. Dup (4p) trisomy was originally described by Wilson et al. [1970: Am J Hum Genet 22:679-690] in a similar case with the same chromosome 4 inversion. To date, at least 85 cases of dup (4p) syndrome have been published, mostly due to unbalanced translocations. Recent articles suggest that the phenotype is hard to recognize clinically due to the lack of specificity of findings. In contrast, 4p trisomy due to an unbalanced pericentric inversion of chromosome 4(p14q35), i.e., the recombinant 4 syndrome observed in our patient, appears to be a discrete entity with relatively consistent features. In total there are four other kindreds described in the literature with this inversion, and the phenotype seems recognizable. Thus, we suggest that recombinant 4 syndrome is a discrete entity among 4p trisomy patients.

Abnormalities, Multiple↗
PubMed2002

De novo pericentric inversion of chromosome 4, inv(4)(p16q12) in a boy with piebaldism and mental retardation.

An 8-year-old boy who was diagnosed to have piebaldism had moderate growth and mental retardation. Chromosome analysis from peripheral blood showed pericentric inversion 4(p16q12). The inversion was further confirmed by fluorescence in situ hybridization using whole chromosome painting and centromeric probes. Chromosomal analysis of parents revealed de novo inheritance of this inversion. This is the first report of pericentric inversion associated with piebald trait.

Child↗
PubMed1993

Pericentric inversion of chromosome 4 giving rise to dup(4p) and dup(4q) recombinants within a single kindred.

Theoretically, every pericentric inversion can give rise, during meiosis, to 2 alternate recombinant chromosomes. One of these will have a duplication of short arm material and deletion of long arm material (dup p), and the other, a duplication of a long arm material and deletion of short arm material (dup q). However, most published cases have been limited to a single recombinant type occurring within a given kindred. Here we document a large pericentric inversion of chromosome 4 which gave rise, within 2 generations of a kindred, to both dup p and dup q recombinants. The family was ascertained by the birth of a baby girl with multiple congenital anomalies suggestive of Wolf-Hirschhorn syndrome, and was found to have a dup 4q recombinant. Subsequent studies of her father and of her 27-year-old mentally retarded aunt showed a balanced inv(4) (p15.32q35) and a dup 4p recombinant, respectively. Given that: (a) the balanced inversion involves approximately 87% of the length of chromosome 4; (b) the predicted meiotic pairing would be homosynapsis with loop formation; (c) the size of the segments distal to the breakpoints of the inversion are of similar and relatively small size; and (d) both recombinants are compatible with life, then the risk for recurrence of a recombinant in this family is high. Genetic counseling addressed these issues, and to date, both chronic villus sampling (CVS) and amniocentesis have been provided for prenatal diagnosis.

Abnormalities, Multiple↗
PubMed1994

Three unrelated cases of paracentric inversions of 1p in individuals with abnormal phenotypes.

Paracentric inversions, involving a rearrangement within one chromosome arm, are rare. Although carriers of balanced paracentric inversions should theoretically not be at risk for abnormal offspring, such cases have been reported. We report on 2 unrelated cases of inherited paracentric inversions of 1p with breakpoints at p32 and p36.1 and p32.3 and p36.22 in individuals with abnormal phenotypes. Another case of 2 abnormal monozygotic twins with a de novo paracentric inversion of 1p with breakpoints at p22 and p34 is presented as well.

Abnormalities, Multiple↗