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PubMed1997

Puerperal inversion of the uterus in Nepal: case reports and review of literature.

Retrospective study of 6 cases of puerperal inversion of the uterus is being presented from 1975 to 1995 and a review of literature for 20 years of the period 1975-1995 has been summarised. In the present series, one case with acute puerperal inversion of uterus were treated by manual reposition, 2 cases of chronic puerperal inversion of uterus was treated surgically by Kustner's vaginal approach. Two cases with subacute puerperal inversion of uterus, 1 case of chronic puerperal inversion were treated by Haultain and Huntington method. Out of 241 cases of uterine inversion obtained from review of literature for last 20 years, 229 (95%) constituted puerperal and 12 (5%) were non puerperal inversions. Among puerperal inversions, 191 (83.4%) cases were of acute type and only 6 (2.62%) cases were of subacute variety. The chronic puerperal inversion constituted 32 (13.9%). Out of 63 cases of uterine inversions in India, maternal deaths were reported as 6 (9.5%) but there was no maternal death in the present series.

Adult↗
PubMed1988

The inverse problem in electrocardiography: solutions in terms of epicardial potentials.

The objective of the inverse problem in electrocardiography is to recover noninvasively regional information about intracardiac electrical events from electrical measurements on the body surface. The choice of epicardial potentials as the solution to the inverse problem is motivated by the availability of a unique epicardial potential solution for each body surface potential distribution, by the ability to verify experimentally the inverse-recovered epicardial potentials, by the proven relationship between epicardial potentials and the details of intracardiac regional events, and by the possibility of using the inverse solution as a supplement or possible replacement to clinical epicardial potential mapping prior to surgical intervention. Although, in principle, the epicardial potential distribution can be recovered from the body surface potential distribution, the inverse problem in terms of potentials is ill-posed, and naive attempts to reconstruct the epicardial potentials result in incorrect solutions which are highly oscillatory. Large deviations from the actual solution may result from inaccuracy of the data measurement, incomplete knowledge of the potential data over the entire torso, and inaccurate description of the inhomogeneous torso volume conductor. This review begins with a mathematical and qualitative description of the inverse problem in terms of epicardial potentials. The ill-posed nature of the problem is demonstrated using a theoretical boundary value problem. Effects of inaccuracies in the body surface potential data (stability estimates) are introduced, and a sensitivity analysis of geometrical and inhomogeneity parameters is presented using an analytical eccentric spheres model. Various computational methods for relating epicardial to body surface potentials, i.e., the computation of the forward transfer matrix, are described and compared. The need for regularization of the inverse recovery of epicardial potentials, resulting from the need to invert the ill-conditioned transfer matrix, is demonstrated. Several regularization techniques are compared in terms of their performance regarding noise in the data and inaccuracies in geometry and inhomogeneities. Finally, several existing, regularized inverse procedures that compute epicardial potentials from measured body surface potential data are introduced and compared. The review concludes with a section that points toward future directions for improving the quality of the inverse-reconstructed epicardial potentials. Future directions for the use of the inverse problem to obtain epicardial potential distributions noninvasively in both experimental animals and patients in a clinical se

Animals↗
PubMed1987

Pericentric inversions in man: personal experience and review of the literature.

The Leuven cytogenetic centre experience on pericentric inversion in man is discussed with exclusion of the pericentric inversions of the heterochromatic blocks of chromosomes 1 and 9. In a total of 51,500 patients, referred for constitutional chromosome analysis during the period 1970-1985, pericentric inversions were found in 24 index patients. The breakpoints detected in these different pericentric inversions are summarized and compared to those found in previous reports. Bands 2p13, 2q21, 5q31, 6q21, 10q22, and 12q13 were shown to be repeatedly involved in the different studies and, furthermore, breakpoints at bands 2q11, 5p13, 5p15, 5q13, 7q11, 11q25, and 14p11 were present in this study as well as in our previous review on reciprocal autosomal translocations. In 13 familial pericentric inversions, even after exclusion of all inversion carrier probands, a 1.6:1 excess of pericentric inversion carriers versus karyotypically normal progeny was observed. While chromosomally unbalanced offspring represent 3.5% of all chromosomally investigated liveborns of the present study, 7.1% of all liveborn inversion carrier offspring presented with a mental retardation and/or multiple congenital anomalies (MR/MCA) problem. Additional chromosomal abnormalities, i.e. a 21 trisomy and an accessory small ring chromosome were observed in two pericentric inversion carriers. These data and results are discussed and compared to the data available in the literature.

Chromosome Banding↗
PubMed1976

Geographical variability in the pericentric inversion system of the grasshopper Trimerotropis pseudofasciata.

Island and mainland populations of Trimerotropis pseudofasciata from California were compared with respect to the nature and extent of their percentric inversion systems. Island populations generally have more chromosomes polymorphic for centromere position than mainland populations and a considerably higher percentage of the genome in these island populations is in a structurally heterozygous state. Thus, although geographically peripheral, the islands provide habitats capable of supporting denser and more chromosomally polymorphic populations than the mainland. Chiasmata are generally localized to terminal positions in all classes of chromosomes and do not occur in the inverted regions of inversion heterozygotes. Chiasma frequency is highest in inversion homozygotes. It is hypothesized that the inversion system in T. pseudofasciata serves the dual synergistic function of preserving allelic sequences in the inversion region intact through inversion heterozygosity and limiting the generation of variability in regions outside the inversion by increasing terminal chiasmata. Additionally, it is argued that it is the gene sequence on only the inversion chromosome that is important in Trimerotropis. This condition contrasts with the "co-adapted" pattern seen in Drosophila where the gene sequences on both chromosomes in the inversion heterozygote are simultaneously important.

Animals↗
PubMed1991

Limits of the distal inversion in the t complex of the house mouse: evidence from linkage disequilibria.

The suppression of crossing-over and the consequent linkage disequilibrium of genetic markers within the t complex of the house mouse is caused by two large and two short inversions. The inversions encompass a region that is some 15 centiMorgans (cM) long in the homologous wild-type chromosome. The limits of the proximal inversions are reasonably well-defined, those of the distal inversions much less so. We have recently obtained seven new DNA markers (D17Tu) which in wild-type chromosomes map into the region presumably involved in the distal inversions of the t chromosomes. To find out whether the corresponding loci do indeed reside within the inversions, we have determined their variability among 26 complete and 12 partial t haplotypes. In addition, we also tested the same collection of t haplotypes for their variability at five D17Leh, Hba-ps4, Pim-1, and Crya-1 loci. The results suggest that the distal end of the most distal inversion lies between the loci D17Leh467 and D17Tu26. The proximal end of the large distal inversion was mapped to the region between the D17Tu43 and Hba-ps4 loci, but this assignment is rather ambiguous. The loci Pim-1, Crya-1, and the H-2 complex, which have been mapped between the Hba-ps4 and Grr within the large distal inversion, behave as if they recombine from time to time with their wild-type homologs.

Animals↗
PubMed1980

Variation in activities of amylase allozymes associated with chromosome inversions in Drosophila pseudoobscura, D. persimilis and D. miranda.

Different electrophoretic alleles of amylase show associations with particular chromosome 3 inversions in D. pseudoobscura and D. persimilis. Relative adult amylase activities were compared in 37, 37 and 10 strains of D. pseudoobscura, D. persimilis and D. miranda, respectively. Strains carrying the same electrophoretic allele were compared by crossing these lines individually to a reference strain carrying a different electrophoretic mobility allele. This procedure allows comparisons among species, inversions, electromorphs and strains for genetic variation in amylase activity. F2 analysis established that the activity variation co-segregates with the structural amylase locus. This type of variation could be due to either structural gene differences or differences in closely linked, cis-acting regulatory regions. Variation has been detected among and within electrophoretic mobility classes. Moreover, this variation is clearly nonrandom and reveals more of the genetic structure associated with the chromosomal inversion phylogeny of D. pseudoobscura and D. persimilis. ----Some of the findings are: (1) Similar electromorphs in D. pseudoobscura and D. persimilis usually show different activities. These species show nearly complete differentiation of amylase alleles, based on activities. (2) D. persimilis has the broadest range of variation in amylase activity, about four-fold between the highest and lowest alleles. D. pseudoobscura and D. miranda are also polymorphic for activity, but have more constrained ranges of variation. D. miranda alleles show on the average about four times the activity of D. pseudoobscura alleles. (3) Some association of electrophoretic mobility and activity has been found. Alleles 1.09 of D. persimilis, as well as 1.43 and 1.55 of D. miranda, have relatively high activity. It may be that these high activity alleles are part of an adaptation to cooler habitats. (4) Within electrophoretic classes, associations of activities with inversions have been found. These are especially strong in D. persimilis. The 1.00 alleles in the ST, KL, MD and WT inversions, the 0.92 allele in the ST and MD inversions and the 1.09 allele in the WT and KL inversions have levels of activities that depend upon the arrangement in which they are located. These results demonstrate that suppression of recombination in inversion heterokaryotypes can result in extensive genic divergence between inversions.

Amylases↗
PubMed2025

Cosmopolitan inversions have a major impact on trait variation and the power of different GWAS approaches to identify associations.

The ability of genomic inversions to reduce recombination and generate linkage can have a major impact on genetically based phenotypic variation in populations. However, the increase in linkage associated with inversions can create hurdles for identifying associations between loci within inversions and the traits they impact. As a consequence, the role of inversions in mediating genetic variation in complex traits remains to be fully understood. This study uses the fruit fly Drosophila melanogaster to investigate the impact of inversions on trait variation. We tested the effects of common inversions among a diverse assemblage of traits including aspects of behavior, morphology, and physiology, and identified that the cosmopolitan inversions In(2L)t and In(3R)Mo are associated with many traits. We compared the ability of different approaches of accounting for relatedness and inversion presence during genome-wide association to identify signals of association with SNPs. We report that commonly used association methods are underpowered within inverted regions, while alternative approaches such as leave-one-chromosome-out improve the ability to identify associations. In all, our research enhances our understanding of inversions as components of trait variation and provides insight into approaches for identifying genomic regions driving these associations.

Drosophila melanogaster↗
PubMed1994

[Variability of inversion polymorphism in populations of Drosophila lummei, Hackman].

Comparison of inversion polymorphism in Drosophila lummei populations from Finland (Kemi) and Russia (Rybnyi) revealed additional species-specific paracentric inversions in chromosomes 2-4. The newly found inversions, 2V, 3M, 4U, and V, were reported only for the Russian population. The 2U inversion had been earlier detected in D. lummei and in the second chromosome of a D. ezoana population from Kamchatka. Species-specific 5T inversion from the Finland population was not found in the Russian population. 4R, S, and 5S inversions were common for both populations but had different sample frequencies. 4R and 5S inversions were more frequent in the Finland, and 4S in the Russian population which may indicate their different adaptive values in these areas. All inversions except 3M were localized in subterminal chromosome regions. 3M inversion was localized in the submedian region.

Animals↗
PubMed1997

Mechanistic studies on metabolic chiral inversion of 4-(4-methylphenyl)-2-methylthiomethyl-4-oxobutanoic acid (KE-748), an active metabolite of the new anti-rheumatic agent 2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid (KE-298), in rats.

The chiral inversion properties of 4-(4-methylphenyl)-2-methylthiomethyl-4-oxobutanoic acid (KE-748), an active metabolite of 2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid (KE-298), were compared with those of ibuprofen in rats. After administration of R(-)-[2 alpha-2H]KE-748, S(+)-KE-748 was present in the rat plasma, and the deuterium atoms of the S(+)-enantiomer were almost all replaced by hydrogen atoms. After administration of S(+)-[2 alpha-2H]KE-748, the deuterium content of S(+)-KE-748 in the plasma remained intact. In the in vitro study, using a cell-free system and rat liver homogenates, the chiral inversion of ibuprofen was apparent when both CoA and ATP were present; however, KE-748 was not inverted. In the study on isolated rat hepatocytes, the unidirectional chiral inversion from R(-)-to S(+)-enantiomer was observed for both ibuprofen and KE-748. When R(-)-ibuprofen was incubated with medium and long chain fatty acids (carbon chain length C6 to C16), using isolated hepatocytes, the chiral inversion decreased significantly. On the other hand, when R(-)-KE-748 was incubated with short and medium chain fatty acids (carbon chain length C3 to C8), chiral inversion was inhibited markedly. To induce hepatic microsomal long chain fatty acid CoA ligase, rats were treated with clofibric acid (CF rats). In both in vitro and in vivo experiments on CF rats, chiral inversion from R(-)-to S(+)-ibuprofen was enhanced significantly compared with that in controls, whereas the enhancement was not observed in the case of R(-)-KE-748. There was no influence of benzoic acid, a typical substrate on medium chain fatty acid CoA ligase in the mitochondrial matrix, on chiral inversion of R(-)-ibuprofen, using, isolated hepatocytes. In contrast, the chiral inversion from R(-)-to S(+)-KE-748 was strongly inhibited in the presence of benzoic acid. These results indicate that chiral inversion of R(-)-KE-748 may proceed via formation of the CoA-thioester intermediate with loss of the 2 alpha-methine proton, in a manner similar to that seem with R(-)-ibuprofen. However, the enzymes needed to form CoA-thioester of R(-)-KE-748 differ from those for R(-)-ibuprofen.

Animals↗
PubMed1990

Physiological interpretations based on lumped element models fit to respiratory impedance data: use of forward-inverse modeling.

Respiratory impedance (Zrs) data at lower (less than 4 Hz) and higher (greater than 32 Hz) frequencies require more complicated inverse models than the standard series combination of a respiratory resistance, inertance, and compliance. In this paper, a forward-inverse modeling approach was used to provide insight on how the parameters in these more complicated inverse models reflect the true physiological system. Forward models are set up to incorporate explicit physiological and anatomical detail. Simulated forward data are then fit with identifiable inverse models and the parameter estimates related to the known detail in the forward model. It is shown that inverse fitting of low frequency data alone will not allow a distinction between frequency dependence due to airway inhomogeneities and frequency dependence due to tissue viscoelasticity. With higher frequency data, a forward model based on an asymmetric branching airways network was used to simulate Zrs from 0.1-128 Hz with increasing amounts of nonuniform peripheral airway obstruction. Here, inverse modeling is more amenable to sensibly separating estimates of airway and tissue properties. A key result, however, is that changes in the tissue parameters of an inverse model (which provides an excellent fit to Zrs data) will appropriately occur in response to inhomogeneous alterations in airway diameters only. The apparent altered tissue properties reflect the decreased communication of some tissue segments with the airway opening and not an explicit change at the tissue level. These phenomena present a substantial problem for the inverse modeler. Finally, inverse model fitting of low and high frequency Zrs data simultaneously with a single model is not helpful for extracting additional physiological detail. Instead, separate models should be applied to each frequency range.

Airway Obstruction↗
PubMed1984

Evidence for heterosynaptic pairing of the inverted segment in pericentric inversion heterozygotes of the deer mouse (Peromyscus maniculatus).

Silver-stained pachytene cells of male deer mice, Peromyscus maniculatus, which were heterozygous for a naturally occurring pericentric inversion of chromosome 6, were analyzed by light microscopy. The presence of the terminally positioned inversion, involving approximately 30% of the length of chromosome 6, was detected by G-banding. Within the inversion, C-band-positive heterochromatin was restricted to the centromeric region. Silver-staining of spermatocytes revealed the synaptonemal complexes (SCs) of the autosomal bivalents and the X-Y chromosome association. Pachytene cells were scored for the presence of inversion loops corresponding to the pericentric inversion of chromosome 6. Possible loop 6 configurations were detected in less than 1% of the cells examined, the vast majority of cells having regularly formed autosomal SCs similar to those reported for homomorphic chromosome pairs in other rodent species. It appears, therefore, that in these mice the inverted region of chromosome 6 was heterosynaptic throughout pachytene. Heterosynapsis is hypothesized as a mechanism which might obviate the production of duplication and deletion chromatids expected from crossing-over in pericentric inversion loops. The observation of heterosynaptic pairing in the inverted segment and the hypothesis of inversion heterosynapsis as a mechanism averting gametic loss are consistent with the widespread occurrence of pericentric inversion polymorphisms in P maniculatus and the apparent failure of pericentric inversions to genetically isolate populations of this species.

Animals↗
PubMed1996

Clinical correlates among 49 families with hemophilia A and factor VIII gene inversions.

Inversions between a gene A copy within intron 22 of the factor VIII gene and additional copies outside the factor VIII gene were found in 49 families with hemophilia A. Inversion patterns were that of recombination with a distal gene A copy in 34, a proximal copy in 14, and a third (variant) copy in one. Baseline factor VIII clotting levels were <1% of normal in 43 and 1% in 6. No inversion was detected in 61 other families whose affected members had < or = 1% activity levels nor in 42 families with moderately severe hemophilia A and 2-5% baseline levels. Both high titer and low level alloantibody inhibitors were found in patients with of without an inversion. Of 13 high titer inhibitors, 8 were persistent and 1 of these patients had an inversion. Of 5 that responded to daily factor VIII infusions, 4 were in patients with gene inversions. Of the 49 families with an inversion, the occurrence of hemophilia was isolated in 30 and the mother was a carrier in the 25 in which additional family members were informative. In three of these families with isolated occurrence, the maternal grandmother was a carrier whereas in three others a de novo mutation occurred in the maternal grandfather's factor VIII gene. Screening for gene inversions in patients with severe (or "borderline" severe) hemophilia A provides a direct marker of the mutation in 45% of families. It is useful even if there is no living affected member and in predicting the likely severity of an infant in which there are no reliable baseline clotting activities, including 70% of families with isolated occurrences of hemophilia A.

Blotting, Southern↗
PubMed1981

Human chromosome heteromorphisms in Americans Blacks: II. Higher incidence of pericentric inversions of secondary constriction regions (h).

Eighty normal American blacks were studied by the CBG technique (C-bands by barium hydroxide using Giemsa) for estimation of size and inversion heteromorphism of chromosomes 1, 9, and 16, and the data were compared to those of whites using subjectively defined criteria. Size and inversion heteromorphisms were classified into 5 levels. The frequencies of size hetromorphisms of chromosomes 1 and 16 were 10.63% and 6.88%, respectively, which are not significantly different from those of a normal population of whites. A higher incidence of size heteromorphisms for chromosome 9 was noted in whites (47.5% vs 30%). The frequencies of inversion heteromorphism of chromosomes 1, 9, and 16 were 17.5%, 21.9%, and 0.0%, respectively. Overall, 61 chromosomes were found to have an inversion. Of these, 28 were in chromosome 1, and 33 were in chromosome 9. A higher incidence of inversion heteromorphisms of chromosomes 1 and 9 was noted in American blacks, while no inversions were found in chromosome 16 in either population. A significant association of increased size of the h region with inversion (r = 0.99 P less than 0.01) is demonstrated, ie, enlarged h regions have a higher frequency of inversions.

Adult↗
PubMed1996

The distribution and phylogenetic significance of a 50-kb chloroplast DNA inversion in the flowering plant family Leguminosae.

Species in 9 of the approximately 650 genera of the flowering plant family Leguminosae are known to possess a large (50-kb) inversion in their chloroplast genomes, relative to the gene order found most commonly among land plants. Putatively basal elements of the family have not been surveyed for the inversion, which is unknown outside the legumes. Using a combination of polymerase chain reaction and restriction-mapping approaches employing primers or hybridization probes flanking inversion endpoints, 132 legume genera were screened for the presence of the inversion. The inversion was found to be absent in all taxa from two of the three subfamilies (Mimosoideae and Caesalpinioideae), whereas the inversion was found to be present in most taxa of the third subfamily (Papilionoideae). Two papilionoid tribes, Swartzieae and Sophoreae, were heterogeneous for the inversion, which is consistent with a number of lines of evidence suggesting the polyphyly of these tribes. The 50-kb inversion appears to be a unique event in the evolution of Leguminosae, providing a synapomorphy for a clade that includes most of the Papilionoideae.

Base Sequence↗
PubMed1986

Paracentric inversions in man.

The Leuven cytogenetic center experience on paracentric inversions in man is discussed. From a total of 51,000 patients, referred for constitutional chromosome analysis during the period 1970-1985, paracentric inversions were found in 18 index patients. A puzzling finding is the high incidence (26%) of mental retardation and/or congenital malformation in the inversion carrier offspring of phenotypically normal parents with identical chromosomal rearrangements. There was also a high incidence of early fetal loss in the inversion carrier parents. This finding may be explained by an increase of chromosomally unbalanced gametes which result from crossing-over in the meiotic inversion loop. Finally, the possibility of an increased tendency to non-disjunction in paracentric inversion carrier parents is discussed. The most frequent paracentric inversion was inv(3)(p13p25); it was detected in seven unrelated index patients. According to the present experience and the literature data, the breakpoints in paracentric inversions seem to occur preferentially at 1p22, 1p36, 3p13, 3p25, 7q11, and 7q22 regions.

Centromere↗
PubMed1998

Induction of somatic intrachromosomal recombination inversion events by cyclophosphamide in a transgenic mouse model.

Somatic intrachromosomal recombination (SICR) can result in chromosomal inversion and deletion, mechanisms which are important in carcinogenesis. We have utilised a transgenic mouse model to study SICR inversion events in spleen cells. The transgenic construct is designed so that expression of an Escherichia coli lacZ transgene only occurs in a cell when an SICR inversion event occurs in the region of the transgene. The inversion events can then be detected by histochemical staining of frozen spleen sections for transgene expression and by polymerase chain reaction across the inversion breakpoints. The spontaneous inversion frequency in spleen rose 2-fold from 1.54 +/- 0.24 x 10(-4) (mean +/- SE) in 4-month-old transgenic mice to 3.12 +/- 0.67 x 10(-4) in 22-month-old mice. Four- or 8-month-old mice were treated with a single intraperitoneal injection of cyclophosphamide, with doses ranging from 0.01 to 100 mg/kg. The animals were killed 3 days after treatment. A significant induction of SICR inversions was detected at all doses with a 3.2-fold maximum induction of inversions detected at 10 mg/kg. These results suggest that the transgenic mouse model used here may be a sensitive model for studying the role of SICR in mutation and in studying risk assessment of environmental DNA-damaging agents.

Animals↗
PubMed1992

A dual level model for speciation by multiple pericentric inversions.

A considerable body of evidence suggests that the deleterious meiotic effects of pericentric inversions in F1 hybrids can be overcome by changes in chiasma location and various means of non-homologous pairing. Such overriding mechanisms may render pericentric inversions benign and increase the likelihood of their fixation in population isolates. It has been argued that overriding mechanisms of this type negate the involvement of pericentric inversions as reproductive isolating mechanisms in speciation. It is suggested, however, that the involvement of pericentric inversions in speciation should be considered on two levels. First, that by reducing meiotic effects in F1 hybrids, overriding mechanisms facilitate the fixation of pericentric inversions. Secondly, when contact hybridization occurs between the chromosomally derived and parental populations second-level effects may be encountered. That is, the recombinational effects of pericentric inversion differences on coadapted gene complexes (sensu Brncic, 1954, Shaw & Coates, 1983) enforce profound inviability barriers in F2 and backcross matings. In this way, multiple pericentric inversions may act as significant post-mating isolating mechanisms, whereas individual inversions with less significant second-level effects may not.

Animals↗
PubMed1992

Chloroplast DNA inversions and the origin of the grass family (Poaceae).

The phylogenetic affinities of the grass family (Poaceae) have long been debated. The chloroplast genomes of at least some grasses have been known to possess three inversions relative to the typical gene arrangement found in most flowering plants. We have surveyed for the presence of these inversions in grasses and other monocots by polymerase chain reaction amplification with primers constructed from sequences flanking the inversion end points. Amplification phenotypes diagnostic for the largest inversion (28 kilobase pairs) were found in genera representing all grass subfamilies, and in the nongrass families Restionaceae, Ecdeiocoleaceae, and Joinvilleaceae, but not in any other monocots--notably, Flagellariaceae, Anarthriaceae, Cyperaceae, or Juncaceae. This finding is consistent with one of the two principal views of grass phylogeny in suggesting that Poaceae and Cyperaceae (sedges) are not closest relatives. A second (approximately 6 kilobases) inversion appears to occur in a subset of the families possessing the 28-kilobase inversion and links Joinvilleaceae and Poaceae, while the smallest inversion appears unique to grasses. These inversions thus provide a nested set of phylogenetic characters, indicating a hierarchy of relationships in the grasses and allies, with Joinvilleaceae identified as the likely sister group to the Poaceae.

Base Sequence↗