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PubMed1996

Sequence analysis of the chromosomal region around and within the V-1-encoding gene of Mycoplasma pulmonis: evidence for DNA inversion as a mechanism for V-1 variation.

Although the variation of V-1 antigens of Mycoplasma pulmonis has been correlated with variable expression of the cytadherence properties of this organism and has been implicated as a virulence determining factor in M. pulmonis-induced murine respiratory disease, the precise function of these antigens remains unknown. We have cloned and characterized genes encoding V-1 from two M. pulmonis UAB CT V-1 variants that differ in hemadsorption properties. A comparison of the nucleotide sequences revealed that these two variant genes were identical in the 5'-most 724 nucleotides. Regions of extensive divergence that contained repeated sequences were found 3' to this conserved region. On the basis of their deduced amino acid sequences, one variant expressed a V-1 protein of 94.2 kDa presumptively containing 40 repeats of 17 amino acids and the other expressed a protein of 27.4 kDa consisting 2 direct, noncontiguous 9-amino-acid repeats. These general properties, as well as the presence of a prokaryotic lipoprotein acylation sequence (L-X-Y-C), indicated that the genes encoding V-1 were similar in structure to genes encoding other mycoplasma surface lipoproteins. Further analysis of sequences flanking these genes revealed that these variants arose via an inversion event which provided an interchange of the two variable regions as well as for the conserved region of these genes and immunoblot analyses using rabbit polyclonal antibodies specific for synthetic peptides derived from the sequences of the different variable regions indicated that DNA inversion acted as a switch which allowed only one of the two different genes to be expressed at any given time. This inversion model clearly provides a mechanism by which M. pulmonis can alter its surface architecture and also strongly suggests that the as-yet-undefined function of V-1 residues in the variable carboxy region of these proteins.

Amino Acid Sequence↗
PubMed2003

Plasma interleukin-12 in malaria-tolerant papua new guineans: inverse correlation with Plasmodium falciparum parasitemia and peripheral blood mononuclear cell nitric oxide synthase activity.

Interleukin-12 (IL-12) has been inversely associated with disease severity in human and murine malaria, and a polymorphism in the IL-12 p40 subunit gene (IL12B) has been associated with susceptibility to human cerebral malaria and reduced nitric oxide (NO) production. To better define the relationships between IL-12, NO, malaria parasitemia, and IL12B polymorphisms during malarial tolerance, plasma IL-12 levels and peripheral blood mononuclear cell NO synthase (NOS) activity were measured in asymptomatic Papua New Guineans exposed to intense malaria transmission. The IL-12 level was strongly inversely correlated with the density of Plasmodium falciparum parasitemia (rho = -0.45; P < 0.001) and was predicted to decrease by 19% (95% confidence interval [CI], 10 to 27%) for each twofold increase in P. falciparum parasitemia. This is consistent with a suppressive effect of parasitemia on IL-12 production, an effect previously shown in vitro and in rodent models of disease. The IL-12 level was inversely correlated with NOS activity (r = -0.22; P = 0.007), with each twofold increase in NOS activity being predictive of a 25% (95% CI, 7 to 38%) decrease in plasma IL-12 levels. This probably reflects additional down-regulation of IL-12 by the high basal NO production and monocyte NOS expression found in the malaria-tolerant state. Neither the IL-12 level nor NOS activity was associated with either of two IL12B polymorphisms, reflecting the diversity of genetic control over immune responses in different populations.

Adolescent↗
PubMed1980

Intramolecular transposition and inversion in plasmid R6K.

Selection was made in Escherichia coli K-12 recA hosts carrying plasmid R6K for ampicillin hyperresistance. Twenty-two selected strains were found to carry mutant plasmids, which, from electron microscopy and restriction enzyme analysis, were concluded to arise by a duplication of transposon Tn2660, which confers ampicillin resistance, in all cases the duplicate transposon being in an inverted orientation with respect to the resident Tn2660. A mutant of R6K, pSJC301, which was temperature sensitive for ampicillin resistance was produced by in vitro hydroxylamine treatment of R6K deoxyribonucleic acid. A plasmid hybrid, pSJC102, was constructed by cloning the EcoRI R6K fragment carrying the wild-type beta-lactamase gene into the EcoRI site of ColE1. pSJC301 and pSJC102 were transformed into the same recA host strain to form a stable biplasmid strain. Ampicillin-hyperresistant mutants were selected from this strain and screened for plasmids with a duplication of transposon Tn2660, which occurred with equal frequency in either pSJC301 or pSJC102; of 12 characterized, all were inverse repeats of the resident transposon. All six Tn2660 inserts into pSJC301 determined temperature-sensitive ampicillin resistance, and all six inserts into pSJC102 determined wild-type ampicillin resistance, from which it was inferred that transposition of a duplicate Tn2660 occurs predominantly as an intramolecular event, at least in the multicopy R6K plasmid. In all 28 insertion mutants of R6K, there was an inversion of the deoxyribonucleic acid between the two transposons, whereas in only one of six insertion mutants of pSJC102, inversion had occurred. These results are discussed in terms of current models of transposition.

Ampicillin↗
PubMed1991

Nucleotide sequence analysis of the inversion termini located within IS3 elements alpha 3 beta 3 and beta 5 alpha 5 of Escherichia coli K-12.

This paper presents the first detailed structural analysis of termini of an inversion mediated by recombination between Escherichia coli native IS elements. The complete nucleotide sequence of the inversion termini in the lactose region of Escherichia coli K-12 confirms our previous suggestion that the inversion occurred by homologous recombination between alpha 3 beta 3 and beta 5 alpha 5 IS3 elements (D. J. Savic, J. Bacteriol. 140:311-319, 1979; D. J. Savic, S. Romac, and S. D. Ehrlich, J. Bacteriol. 155:943-946, 1983). The data show a slight structural divergence of alpha 3 beta 3 and beta 5 alpha 5 elements, but they do not reveal new sequences within recombined IS3 elements that could influence the expression of nearby genes.

Base Sequence↗
PubMed1991

Structure of the gas vesicle plasmid in Halobacterium halobium: inversion isomers, inverted repeats, and insertion sequences.

Halobacterium-halobium NRC-1 harbors a 200-kb plasmid, pNRC100, which contains a cluster of genes for synthesis of buoyant gas-filled vesicles. Physical mapping of pNRC100 by using pulsed-field gel electrophoresis showed the presence of a large (35 to 38-kb) inverted repeat (IR) sequence. Inversion isomers of pNRC100 were demonstrated by Southern hybridization analysis using two restriction enzymes, AflII and SfiI, that cut asymmetrically within the intervening small single-copy region and the large single-copy region, respectively, but not within the large IRs. No inversion isomers were observed for a deletion derivative of pNRC100 lacking one IR, which suggests that both copies are required for inversion to occur. Additionally, the identities and approximate positions of 17 insertion sequences (IS) in pNRC100 were determined by Southern hybridization and limited nucleotide sequence analysis across the IS element-target site junctions: ISH2, a 0.5-kb element, was found in four copies; ISH3, a 1.4-kb heterogeneous family of elements, was present in seven copies; ISH8, a 1.4-kb element, was found in five copies; and ISH50, a 1.0-kb element, was present in a single copy. The large IRs terminated at an ISH2 element at one end and an ISH3 element at the other end. pNRC100 is similar in structure to chloroplast and mitochondrial genomes, which contain large IRs and other large halobacterial and prokaryotic plasmids that are reservoirs of IS elements but lack the large IRs.

Base Sequence↗
PubMed2006

Rapid detection of the Mycobacterium tuberculosis Beijing genotype and its ancient and modern sublineages by IS6110-based inverse PCR.

The Mycobacterium tuberculosis Beijing genotype strains appear to be hypervirulent and associated with multidrug-resistant tuberculosis. Therefore, the development of a both rapid and simple method to detect the M. tuberculosis Beijing genotype is of clinical interest per se. Previously, we described a simple and fast approach to detect the Beijing genotype based on IS6110 inverse-PCR typing. Here, we evaluated this method against a large, diverse, and recent collection of strains. The study sample included 866 M. tuberculosis strains representing but not limited to the regions in Russia, Europe, and East Asia where the Beijing genotype is endemic. Based on a spoligotyping method, 408 strains were identified as Beijing genotypes; they were additionally subdivided into ancient and modern sublineages based on the analysis of the NTF locus. All strains were further subjected to the IS6110-based inverse PCR. All of the Beijing genotype strains were found to have identical two-band (ancient sublineage) or three-band (modern sublineage) profiles that were easily recognizable and distinct from the profiles of the non-Beijing strains. Therefore, we suggest using IS6110-based inverse-PCR typing for the correct identification of the Beijing genotype and its major sublineages. The method is fast and inexpensive and does not require additional experiments but instead is implemented in the routine typing method of M. tuberculosis.

Bacterial Typing Techniques↗
PubMed2005

Long term outcomes of inversion ankle injuries.

BACKGROUND: Ankle sprains are common sporting injuries generally believed to be benign and self limiting. However, some studies report a significant proportion of patients with ankle sprains having persistent symptoms for months or even years. AIMS: To determine the proportion of patients presenting to an Australian sports medicine clinic who had long term symptoms after a sports related inversion ankle sprain. METHODS: Consecutive patients referred to the NSW Institute of Sports Medicine from August 1999 to August 2002 with inversion ankle sprain were included. Exclusion criteria were fracture, ankle surgery, or concurrent lower limb problems. A control group, matched for age and sex, was recruited from patients attending the clinic for upper limb injuries in the same time period. Current ankle symptoms, ankle related disability, and current health status were ascertained through a structured telephone interview. RESULTS: Nineteen patients and matched controls were recruited and interviewed. The mean age in the ankle group was 20 (range 13-28). Twelve patients (63%) were male. Average follow up was 29 months. Only five (26%) ankle injured patients had recovered fully, with no pain, swelling, giving way, or weakness at follow up. None of the control group reported these symptoms (p<0.0001). Assessments of quality of life using short form-36 questionnaires (SF36) revealed a difference in the general health subscale between the two groups, favouring the control arm (p<0.05). There were no significant differences in the other SF36 subscales between the two groups. CONCLUSION: Most patients who sustained an inversion ankle injury at sport and who were subsequently referred to a sports medicine clinic had persistent symptoms for at least two years after their injury. This reinforces the importance of prevention and early effective treatment.

Adolescent↗
PubMed2003

Effect of strength and proprioception training on eversion to inversion strength ratios in subjects with unilateral functional ankle instability.

OBJECTIVES: To examine the effect of six weeks of strength and proprioception training on eversion to inversion isokinetic strength ratios (E/I ratios) in subjects with unilateral functional ankle instability. METHODS: Thirty eight subjects were randomly assigned to one of four treatment groups: strength training (S); proprioception training (P); strength + proprioception training (B); control (C). Isokinetic strength was tested before and after training using a Kin Com 125 automatic positioning isokinetic dynamometer. Subtalar joint eversion and inversion motions were tested both concentrically and eccentrically through a range of motion involving 40 degrees. All peak torque and average torque values were normalised for body mass. E/I ratios were calculated from average torque and peak torque measures by taking the concentric eversion value and combining it with the eccentric inversion value. Data were analysed using a mixed model analysis of variance with repeated measures on the test factor. Average torque and peak torque E/I ratios at 30 and 120 degrees/s were analysed separately. RESULTS: There were no significant differences in average torque and peak torque E/I ratios of the functionally unstable ankle for any of the groups after training compared with before. CONCLUSIONS: Six weeks of strength and proprioception training (either alone or combined) had no effect on isokinetic measures of strength in subjects with self reported unilateral functional instability. Further studies examining this agonist (concentric) to antagonist (eccentric) muscle group strength ratio are needed.

Adult↗
PubMed2004

Dynamic imaging of pancreatic diseases by contrast enhanced coded phase inversion harmonic ultrasonography.

BACKGROUND: Coded phase inversion harmonic ultrasonography, a newly available sonographic technique, enables visualisation of slow flow in minute vessels in a real time fashion with the use of a sonographic contrast agent containing monosaccharide. Our purpose was to employ this novel technique to observe microvessels in pancreatic tumours. SUBJECTS AND METHODS: Sixty five patients with suspicious pancreatic tumours received contrast enhanced coded phase inversion harmonic ultrasonography, contrast enhanced computed tomography, and endosonography. Final diagnoses based on histological findings were pancreatic ductal carcinomas in 49 patients, inflammatory pseudotumours with chronic pancreatitis in seven, and endocrine tumours in nine. For contrast enhanced coded harmonic ultrasonography, Levovist, a contrast agent, was injected intravenously as a bolus. When the first microbubble signal appeared in the pancreas, images of the ideal scanning plane were displayed in a real time continuous fashion (vessel images). Subsequently, interval delay scanning (perfusion images) was taken to demonstrate parenchymal flow. Tumour vascularity was evaluated by using the two types of imaging. Sensitivities for depicting pancreatic tumours were compared between three examinations. RESULTS: Contrast enhanced ultrasonography demonstrated tumour vessels in 67% of pancreatic ductal carcinomas, although most were relatively hypovascular compared with the surrounding pancreatic tissue. The vascular patterns of tumours obtained by contrast enhanced ultrasonography were closely correlated with those obtained by contrast enhanced computed tomography. Values for sensitivity in depicting pancreatic tumours of 2 cm or less in size were 68% for contrast enhanced computed tomography, 95% for endosonography, and 95% for contrast enhanced ultrasonography. CONCLUSION: Contrast enhanced coded phase inversion harmonic ultrasonography successfully visualised fine vessels in pancreatic tumours and may play a pivotal role in the depiction and differential diagnosis of pancreatic tumours.

Adult↗
PubMed2005

An immunohistochemical analysis to evaluate an inverse correlation between Runx2/Cbfa1 and NF kappa B in human osteosarcoma.

BACKGROUND: Dominant negative inhibition of nuclear factor kappa B (NF kappa B) signalling activity in a human osteosarcoma cell line (Saos2) results in malignant reversion and the induction of the osteoblast differentiating transcription factor, Runx2/Cbfa1. This observation suggests that there is an inverse relation between a transcription factor associated with malignant progression and chemoresistance (NF kappa B) and an osteoblast differentiating transcription factor (Runx2/Cbfa1). AIMS: To assess and correlate Runx2/Cbfa1 and NF kappa B (p65) immunoreactivity in human osteosarcoma. METHODS: Runx2/Cbfa1 and NFkappaB (p65) immunoreactivity was assessed on 11 paraffin wax embedded archival specimens of human primary osteosarcoma by standard immunohistochemical methods and scored on a scale of 0-3. A Pearson correlation analysis between Runx2/Cbfa1 and NF kappa B (p65) scores was established. RESULTS: Runx2/Cbfa1 was expressed constitutively in all pathology specimens of human osteosarcoma. Of note, a chondroblastic osteosarcoma showed the highest Runx2/Cbfa1 immunoreactivity. A Pearson correlation did not support an inverse correlation between Runx2/Cbfa1 and NF kappa B (p65) scores (r = 0.57) in human osteosarcoma. CONCLUSION: Runx2/Cbfa1 immunoreactivity does not inversely correlate with NF kappa B immunoreactivity, and thus cannot serve as an indirect measure of NF kappa B activity or an independent predictive or prognostic indicator.

Biomarkers, Tumor↗
PubMed2000

The "inverse housing law" and respiratory health.

STUDY OBJECTIVE: To investigate whether there is a mismatch within Britain between climate severity and housing quality ("inverse housing law") and whether this mismatch is associated with respiratory health. DESIGN, SETTING AND PARTICIPANTS: Cross sectional observational study. Britain (Scotland, Wales and England). The 3023 male and 3694 female Health and Lifestyle Survey participants with valid data available on all relevant items. MAIN RESULTS: Geographical mapping shows a mismatch between climate severity and housing quality. Individual level analysis shows that lung function is associated with climate and housing, and their interaction, independently of cigarette smoking status. The physical quality of the housing seems to be most important to respiratory health in areas with harsh climate. CONCLUSIONS: Interpretation must be cautious because cross sectional data have been used to investigate processes that are longitudinal and, possibly, selective. Nevertheless, there does seem to be an "inverse housing law", such that some of the worst quality housing is found in areas with severe climate; and, on the balance of probabilities, this inverse housing law affects respiratory health.

Climate↗
PubMed1988

Short-Ti inversion-recovery pulse sequence: analysis and initial experience in cancer imaging.

Inversion recovery (IR), commonly considered a pulse sequence capable of producing T1-weighted images with excellent display of normal anatomy, is versatile: The null point and peak time provide a useful, succinct summary of the properties of IR and its capacity for producing both T1- and T2-weighted images. Shortening of the inversion time (TI) and creation of a short-TI inversion-recovery (STIR) pulse sequence increases sensitivity to malignancy and other abnormalities by making the effects of prolonged T1 and T2 on signal intensity additive and by nulling the signal from fat. The authors examined over 300 patients with various malignancies and compared STIR images with T1- and T2-weighted images obtained at 0.5 T. In 43 cases, signal-difference-to-noise ratios (SD/Ns) were calculated between tumor, fat, and muscle. In general, STIR images demonstrated tumor as a conspicuously high-intensity area in a background of muted, discernible anatomic detail. The good contrast achieved with STIR sequences between tumor and fat (SD/N = 18.1) and tumor and muscle (SD/N = 12.9) consolidated into a single image the information contained separately on T1- and T2-weighted images, which facilitates efficient detection and localization of malignancy.

Adipose Tissue↗
PubMed1996

"Black blood" T2-weighted inversion-recovery MR imaging of the heart.

PURPOSE: To develop a short-inversion-time inversion-recovery (STIR) magnetic resonance imaging pulse sequence for evaluating the myocardium that is relatively free of flow and motion artifact. MATERIALS AND METHODS: The authors implemented a breath-hold, cardiac-triggered STIR sequence with preparatory radio-frequency pulses to eliminate signal from flowing blood. A segmented rapid acquisition with relaxation enhancement (turbo spin echo) readout was used, with the inversion-recovery delay adjusted to null fat. The sequence was implemented at 1.0 and 1.5 T and tested in phantoms, five healthy volunteers, and three patients. RESULTS: Phantom studies confirmed the expected behavior of the sequence. In the volunteers, fat-suppressed images of the heart with STIR contrast were generated in a breath-hold period. Blood in the heart chambers was uniformly nulled, and motion artifacts were effectively suppressed. Focal high signal intensity consistent with edema was seen in two patients with acute myocardial infarction; in a third patient, a paracardiac mass was visualized and sharply demarcated relative to normal myocardium. CONCLUSION: Fast STIR imaging of the heart with effective suppression of flow and motion artifacts was implemented. The approach has much potential for high-contrast imaging in a variety of diseases affecting the heart and mediastinum.

Adult↗
PubMed1997

Breast-conserving radiation therapy: potential of inverse planning with intensity modulation.

PURPOSE: To evaluate inverse planning with beam-intensity modulation in breast-conserving radiation therapy. MATERIALS AND METHODS: A prototype inverse treatment-planning system was used in five patients with early-stage breast tumors. The prescription for the breast was 5,040 cGy in 180-cGy fractions, with the primary tumor site receiving 6,000 cGy in 214-cGy fractions. Isodose distributions from the prototype were compared section by section with those from conventional three-dimensional planning. RESULTS: The inverse planning system showed dose variation of 84%-98% to 111%-113% in the primary tumor site. For whole-breast irradiation, 95% of the target volume received at least 4,000 cGy. High-dose areas were adjacent to the primary site. Lower-dose areas were in the most medial part of the breast. Compared with the conventional system, target doses were similar. The volume of lung and heart that received high doses was smaller; however, larger lung and heart volumes received doses of less than 1,200 cGy. CONCLUSION: Intensity modulation may accomplish "concomitant boost" treatment. Acceptable dose gradients are achieved in the target volumes, with lower volumes of high-dose treatment in normal tissue. Plans that required comprehensive nodal radiation, in particular, were improved relative to conventional plans. Optimization of the planning system is needed to minimize the lung and heart volumes that receive low-dose radiation.

Breast↗
PubMed2000

Hepatic tumors: contrast agent-enhancement patterns with pulse-inversion harmonic US.

PURPOSE: To evaluate contrast agent-enhancement patterns in hepatic hemangiomas, hepatic metastases, and hepatocellular carcinomas (HCCs) at pulse-inversion harmonic ultrasonography (US) with a microbubble contrast agent. MATERIALS AND METHODS: Twenty hepatic hemangiomas in 20 patients and 41 malignant hepatic tumors in 23 patients (33 metastases and eight HCCs) were evaluated with pulse-inversion harmonic US. US images were obtained before injection and every 10-15 seconds after injection of a 4-g bolus (300 mg/mL) of SH U 508A (a microbubble contrast agent) for 5 minutes. The contrast-enhancement patterns of 61 hepatic lesions were assessed. RESULTS: Of 20 hemangiomas, 19 revealed peripheral enhancement, which was globular in 14 (70%) and rimlike in five (25%), with centripetal fill-in; the remaining one (5%) showed homogeneous enhancement. In 33 metastases, the enhancement was rimlike in 16 (48%), homogeneous in seven (21%), and stippled in two (6%); in the remaining eight metastases (24%), no enhancement was seen. Of eight HCCs, four (50%) showed homogeneous enhancement and the remaining four (50%) showed heterogeneous enhancement. Centripetal fill-in of lesions with intratumoral enhancement was not seen in any malignancy. CONCLUSION: Pulse-inversion harmonic US with a microbubble contrast agent is potentially useful for the specific diagnosis of hemangiomas that demonstrate characteristic enhancement features.

Adult↗
PubMed2000

Hepatic malignancies: improved detection with pulse-inversion US in late phase of enhancement with SH U 508A-early experience.

Twenty consecutive patients with known liver malignancies underwent ultrasonography (US) in conventional B mode and in pulse-inversion mode in the late hepatic-specific parenchymal phase after intravenous administration of SH U 508A, a microbubble US contrast agent. Two experienced readers assessed subjective and objective conspicuity, number of lesions, and smallest lesion diameter in each mode. Subjective and objective conspicuity were improved with pulse-inversion mode, and smaller lesions were depicted with pulse-inversion mode than with conventional B mode, improving the detection of metastases less than 1 cm in size.

Adult↗
PubMed1998

Beta-adrenergic receptor number in human lymphocytes is inversely correlated with aerobic capacity.

In the present study, the relationships between beta-adrenergic receptor (beta-AR) expression and aerobic capacity evaluated by maximal oxygen consumption (.VO2max) and oxygen consumption level at ventilatory threshold (.VO2@VT) were investigated. Seventeen physically untrained and 25 trained men participated in the study. After supine resting, the peripheral blood was sampled for preparation of lymphocytes, the model cell used to analyze the beta-AR state. The total number of beta-AR in lymphocytes (beta-ARtotal) was inversely correlated with the VO2 max (r = -0. 368; P < 0.05) and the VO2@VT (r = -0.359; P < 0.05). Similar relationships were also observed between the number of beta-AR in cell surface and both VO2 max (r = -0.491; P < 0.05) and VO2@VT (r = -0.498; P < 0.05). However, no correlation was obtained between the number of beta-AR in intracellular compartments and either VO2 max or VO2@VT. The beta2-AR mRNA level quantified by the use of competitive reverse transcription-polymerase chain reaction was inversely correlated with VO2@VT (r = -0.567; P < 0.05) and positively correlated with beta-ARtotal (r = 0.521; P < 0.05). These findings suggest that the beta-AR number in lymphocytes is inversely correlated with aerobic capacity. This relationship may be explained by downregulation of beta-AR, including internalization with subsequent degradation of the receptors and inhibition of the beta-AR biosynthesis.

Adolescent↗
PubMed2003

Adaptation to stable and unstable dynamics achieved by combined impedance control and inverse dynamics model.

This study compared adaptation in novel force fields where trajectories were initially either stable or unstable to elucidate the processes of learning novel skills and adapting to new environments. Subjects learned to move in a null force field (NF), which was unexpectedly changed either to a velocity-dependent force field (VF), which resulted in perturbed but stable hand trajectories, or a position-dependent divergent force field (DF), which resulted in unstable trajectories. With practice, subjects learned to compensate for the perturbations produced by both force fields. Adaptation was characterized by an initial increase in the activation of all muscles followed by a gradual reduction. The time course of the increase in activation was correlated with a reduction in hand-path error for the DF but not for the VF. Adaptation to the VF could have been achieved solely by formation of an inverse dynamics model and adaptation to the DF solely by impedance control. However, indices of learning, such as hand-path error, joint torque, and electromyographic activation and deactivation suggest that the CNS combined these processes during adaptation to both force fields. Our results suggest that during the early phase of learning there is an increase in endpoint stiffness that serves to reduce hand-path error and provides additional stability, regardless of whether the dynamics are stable or unstable. We suggest that the motor control system utilizes an inverse dynamics model to learn the mean dynamics and an impedance controller to assist in the formation of the inverse dynamics model and to generate needed stability.

Adaptation, Physiological↗