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The physiologic effects of inverse ratio ventilation.

STUDY OBJECTIVES: The efficacy of inverse ratio ventilation in ARDS is not clear. Furthermore, the mechanism responsible has not been determined. We designed an animal study to determine if inverse ratio ventilation improves gas exchange and by what mechanism. DESIGN: Prospective randomized, controlled design was used. SETTING: University of Missouri Pulmonary/Critical Care Animal Laboratory. PARTICIPANTS: Nine dogs with oleic acid-induced lung injury as control animals to assess stability of the model, nine in the experimental model. INTERVENTIONS: Conventional ventilation with full recruitment extrinsic positive end-expiratory pressure (PEEP) was compared with two other modes of ventilation. One was inverse ratio with extrinsic PEEP and the second was inverse ratio with intrinsic PEEP equal to full recruitment PEEP. Full recruitment levels of PEEP were defined by optimizing compliance, then increasing PEEP by 2.5 cm/H2O. Each type of ventilation was maintained for 45 min after the edema had stabilized. Comparison of lung injury over time requires stability of the model over time. Therefore, we also assessed the stability of the preparation over time by examining compliance, extravascular lung water, and venous admixture in nine control dogs with equivalent lung injury over the same time span. MEASUREMENTS AND RESULTS: Mean airway pressure was increased by both types of inverse ratio ventilation, while compliance remained stable. Venous admixture was reduced (conv=0.32+/-0.12, inverse ratio with extrinsic PEEP=0.24+/-0.10, inverse ratio with intrinsic PEEP=0.28+/-0.11) with inverse ratio with extrinsic PEEP, but the improvement was less with inverse ratio with intrinsic PEEP, even though the mean airway pressure was higher. CONCLUSIONS: We conclude that increasing mean airway pressure by prolongation of the inspiratory time improves gas exchange in our model of ARDS, but when mean airway pressure is increased further, allowing the development of intrinsic PEEP, the beneficial effects on gas exchange are less. Increasing mean airway pressure with intrinsic PEEP is not equivalent to other methods of increasing mean airway pressure.

Airway Resistance↗

Phase-inversion sonography during the liver-specific late phase of contrast enhancement: improved detection of liver metastases.

OBJECTIVE: The purpose of our study was to assess whether phase-inversion sonography during the late, liver-specific phase of contrast enhancement using Levovist improves the detection of hepatic metastases relative to unenhanced conventional B-mode sonography. SUBJECTS AND METHODS: Sixty-two patients were studied with unenhanced B-mode sonography and phase-inversion sonography 2.5 min after the injection of Levovist. All patients underwent one reference examination (CT, MR imaging, or intraoperative sonography). The conspicuity, number, size, and distribution of metastases before and after contrast administration as judged by a sonographer (who was unaware of other imaging findings) were compared with each other and with reference imaging. RESULTS: The conspicuity of metastases was improved by contrast-enhanced phase inversion in 94% of patients. Thirty-nine patients showed metastases on reference imaging; 36 of these were positive on baseline sonography and 38 on phase-inversion sonography. Phase-inversion sonography showed more reference imaging-confirmed metastases than baseline sonography in 28 patients (45%). The average number of confirmed metastases per patient was 3.06 for baseline sonography and 5.42 for contrast-enhanced phase-inversion sonography (p < 0.01). The average sensitivity for detecting individual metastases improved from 63% to 91%. Metastases of less than 1 cm were shown in 14 patients on baseline sonography, in 24 patients on phase-inversion sonography, and in 26 on reference imaging. Both sonographic techniques showed false-positive lesions in six patients. CONCLUSION: Contrast-enhanced phase-inversion sonography in the liver-specific phase of contrast enhancement using Levovist provides a marked improvement in the detection of hepatic metastases relative to unenhanced conventional sonography, without loss of specificity. Phase-inversion sonography was particularly advantageous in detecting small metastases and may be a competitive alternative to CT and MR imaging.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Effects of chromosomal inversion on cell fitness in Escherichia coli K-12.

In an effort to learn what factors might mitigate the establishment of Escherichia coli variants bearing major chromosomal rearrangements, we have examined the effects on cell growth of two inversions between rRNA operons. One of these inversions, IN(rrnD-rrnE), had been propagated in a commonly used subline of E. coli K-12 for approximately 30 yr before its discovery, a fact that illustrates the absence of obvious detrimental effects associated with the inversion. We found that culturing under conditions requiring repeated transition from stationary phase to rapid growth led to the replacement of IN(rrnD-rrnE) cells by cells that had undergone either of two types of additional chromosomal inversion: one type fully restored the wild-type order, while the other partially restored it. The partial reinversion was also between rrn operons, but it left a small transposition. The tendency for overgrowth by these revertants persisted through several rounds of periodic selection. In contrast, the other inversion, IN(rrnG-rrnE), was associated with severe, detrimental effects. The effects of IN(rrnG-rrnE) were also alleviated by full or partial reinversion. The probable relationship between the severity of the effects caused by the inversions and the degree of displacement of the replication origin is discussed. Spontaneous inversion events between rrn operons separated by 18% of the chromosome were estimated to occur at a frequency of roughly 10(-5). If extended to natural situations, the growth disadvantage together with the relatively high frequency of reinversion suggest that clones of cells with an inversion between these rrn operons would be readily overgrown by revertants.

Chromosome Inversion↗

Multiple origins of cytologically identical chromosome inversions in the Anopheles gambiae complex.

For more than 60 years, evolutionary cytogeneticists have been using naturally occurring chromosomal inversions to infer phylogenetic histories, especially in insects with polytene chromosomes. The validity of this method is predicated on the assumption that inversions arise only once in the history of a lineage, so that sharing a particular inversion implies shared common ancestry. This assumption of monophyly has been generally validated by independent data. We present the first clear evidence that naturally occurring inversions, identical at the level of light microscopic examination of polytene chromosomes, may not always be monophyletic. The evidence comes from DNA sequence analyses of regions within or very near the breakpoints of an inversion called the 2La that is found in the Anopheles gambiae complex. Two species, A. merus and A. arabiensis, which are fixed for the "same" inversion, do not cluster with each other in a phylogenetic analysis of the DNA sequences within the 2La. Rather, A. merus 2La is most closely related to strains of A. gambiae homozygous for the 2L+. A. gambiae and A. merus are sister taxa, the immediate ancestor was evidently homozygous 2L+, and A. merus became fixed for an inversion cytologically identical to that in A. arabiensis. A. gambiae is polymorphic for 2La/2L+, and the 2La in this species is nearly identical at the DNA level to that in A. arabiensis, consistent with the growing evidence that introgression has or is occurring between these two most important vectors of malaria in the world. The parallel evolution of the "same" inversion may be promoted by the presence of selectively important genes within the breakpoints.

Animals↗

Localized remodeling of the Escherichia coli chromosome: the patchwork of segments refractory and tolerant to inversion near the replication terminus.

The behavior of chromosomal inversions in Escherichia coli depends upon the region they affect. Regions flanking the replication terminus have been termed nondivisible zones (NDZ) because inversions ending in the region were either deleterious or not feasible. This regional phenomenon is further analyzed here. Thirty segments distributed between 23 and 29 min on the chromosome map have been submitted to an inversion test. Twenty-five segments either became deleterious when inverted or were noninvertible, but five segments tolerated inversion. The involvement of polar replication pause sites in this distribution was investigated. The results suggest that the Tus/pause site system may forbid some inversion events, but that other constraints to inversion, unrelated to this system, exist. Our current model for deleterious inversions is that the segments involved carry polar sequences acting in concert with other polar sequences located outside the segments. The observed patchwork of refractory and tolerant segments supports the existence of several NDZs in the 23- to 29-min region. Microscopic observations revealed that deleterious inversions are associated with high frequencies of abnormal nucleoid structure and distribution. Combined with other information, the data suggest that NDZs participate in the organization of the terminal domain of the nucleoid.

Chromosome Inversion↗

Rearrangement of the bacterial chromosome: forbidden inversions.

The order of genes in the chromosome of enteric bacteria has been evolutionarily conserved despite the existence of mechanisms for rearrangement. Homologous chromosomal sequences in the same orientation recombine to form deletions or duplications. When homologous sequences in inverse orientation recombine, one expects to form an inversion of the intervening chromosomal segment. This expectation was tested by placing pairs of homologous sequences in inverse order at various points in the chromosome. Sequences at many pairs of sites (permissive) do recombine to generate the expected inversion, while the same sequences placed at other pairs of sites (nonpermissive) do not form an inversion. For the one nonpermissive interval tested, the missing inversion type can be constructed by an alternative transductional method; strains with this inversion are viable. Thus mechanistic limitations must prevent sequences at particular sites from undergoing the recombination event required to form an inversion.

Chromosome Inversion↗

Genetic differentiation and inversion clines in Indian natural populations of Drosophila melanogaster.

To study the genetic differentiation and inversion clines in Indian natural populations of Drosophila melanogaster, 14 natural populations (6 from the north and 8 from the south) were screened for chromosome inversions. The chromosomal analysis revealed the presence of 23 paracentric inversions, which include 4 common cosmopolitan, 4 rare cosmopolitan, 2 recurrent endemic, and 13 unique endemic (new inversions detected for the first time) inversions. The difference in karyotype frequencies between populations from the north and south were highly significant and the level of inversion heterozygosity was higher in populations from the south. Statistically significant negative correlations were found between each of the four common cosmopolitan inversions and latitude. These findings are in accord with results from other worldwide geographic regions and show that Indian populations of D. melanogaster have undergone considerable genetic differentiation at the level of inversion polymorphism.

Animals↗

Uterine inversion: a life-threatening obstetric emergency.

BACKGROUND: Acute puerperal uterine inversion is a rare but potentially life-threatening complication in which the uterine fundus collapses within the endometrial cavity. Although the cause of uterine inversion is unclear, several predisposing factors have been described. Maternal mortality is extremely high unless the condition is recognized and corrected. METHODS: MEDLINE was searched from 1966 to the present using the key phrase "uterine inversion." Nonpuerperal uterine inversion case reports were excluded from review except when providing information on classification and diagnostic techniques. A summarized case involving uterine inversion and a review of the classification, etiology, diagnosis, and management are reported. RESULTS AND CONCLUSIONS: Although uncommon, if left unrecognized, uterine inversion will result in severe hemorrhage and shock, leading to maternal death. Manual manipulation should be attempted immediately to reverse the inversion. Tocolytics, such as magnesium sulfate and terbutaline, or halogenated anesthetics may be administered to relax the uterus to aid in reversal. Intravenous nitroglycerin provides an alternative to the tocolytics and offers several pharmacodynamic advantages. Treatment with hydrostatic pressure may be attempted while waiting for medications to be administered or for general anesthesia to be induced. In the most resistant of inversions, surgical correction might be required.

Adult↗

[The role of inversions in adaptation and speciation].

Studies concerning the effect of population-specific inversions on mating behavior of Drosophila lummei Hackman showed that competitiveness of males carrying the inversion for mating with females without the inversion significantly decreases, independently from the location of inversions in chromosomes and the origin of studied strains. Crossing of the competing males with the female carrying the population-specific inversion showed that the competitiveness of males with the inversion in their genome increases in a series of crosses but, nevertheless, remains lower than that of males without the inversion. Hence, it can be suggested that population-specific inversions can be involved in prezygotic isolation of specific forms during the species divergence.

Adaptation, Physiological↗

Studies on the in vitro inversion of flurbiprofen.

This paper reports in vitro studies on the metabolic inversion of flurbiprofen (FL), an arylpropionic acid antiinflammatory agent (2-APA). The inversion was studied with both rac-FL and R-FL, by incubation with rat hepatic microsomes, in the presence of either CoASH and ATP or NADPH. The two isomers of the drug were separated as their (+)-(R)-1-phenylethylamides by direct phase high-performance liquid chromatography on a silica gel column with an achiral mobile phase. The inversion was more pronounced in the presence of CoASH and ATP for both the racemate and the R-isomer, which supports the key role of CoA thioesters in the metabolic inversion of profens. The inversion observed in the presence of NADPH suggests that, when the incubation is run with hepatic microsomes, a CYP450-mediated pathway is also active. In order to get more insight into the CYP450-mediated inversion pathway, we studied the effect of irradiating microsomes with a low dose of He-Ne laser radiation (0.2 J). Such irradiation caused a significant increase in inversion at all times studied and normalized the anomalous value of inversion observed at 15 min in this pathway.

Animals↗

Preparation of Colloidal Low-Density Polyethylene Latexes by Flow-Induced Phase Inversion Emulsification of Polymer Melt in Water.

The aim of this study is to prepare colloidal polymeric latexes by using the flow-induced phase inversion emulsification method given by G. Akay [Chem. Eng. Sci. 53, 203 (1998)] of polymer melts followed by the solidification of polymer melt droplets. We also investigate the mechanism of emulsification and stabilization in polymeric dispersions which undergo a phase change after emulsification. The history of the emulsification and emulsion structure are monitored by using a process rheometer and off-line scanning electron microscopy with energy-dispersive X-ray analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy, and particle size measurements. It is shown that the molecular structure of the surface-active material is the most important parameter in achieving phase inversion emulsificationin polymer melts. Molecular surfactants could not be used to provide surface activity in polymeric melts. Several experimental polymeric surfactants are used and their ability to form a [water-in-polymer melt] emulsion is tested. The successful polymeric surfactants are known as hydrophobically modified water-soluble polymers. It is postulated that the surface-active materials should conform at the water/polymer melt interface and not be removed from the interface by surface deformations. The ability of hydrophobically modified water-soluble polymers to remain at the interface is reduced if the hydrophobic moeties which anchor into the polymer melt have chain length approaching 18 carbons or more. After the first phase inversion and subsequent dilution of the [polymer melt-in-water], if mixing is carried out while cooling, a second phase inversion takes place from [polymer melt-in-water] to [water-in-solid polymer] despite high water content of the polymer/water system. If the water content is high (25-40% investigated) the second phase inversion yields a powdered material with encapsulated water. A third phase inversion occurs if the powdered microcapsules from the second phase inversion is heated while mixing to yield a [(water-in-polymer)-in-water] multiple emulsion which can be inverted back to [polymer melt-in-water] emulsion by increasing the temperature and subjecting the emulsion to high deformation rate flows. However, if this last phase inversion is not allowed to proceed to completion, and the [(water-in-polymer)-in-water] multiple emulsion is cooled, microporous polymeric particles are obtained. Copyright 2001 Academic Press.

Journal Article↗