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PubMed1995

Gene-centromere mapping of bovine DYA, DRB3, and PRL using secondary oocytes and first polar bodies: evidence for four-strand double crossovers between DYA and DRB3.

A genetic map consisting of three loci anchored at the centromere of bovine chromosome 23 was constructed by genotyping secondary oocytes (SO) and first polar bodies (PB1) using a polymerase chain reaction (PCR)-based approach. Primary oocytes arrested in prophase of meiosis I were stimulated in vitro to resume division and extrude PB1. Sixty SO and their matched PB1 were collected from 14 cows by micro-manipulation, subjected to amplification of the whole genome by primer extension preamplification, and genotyped independently for the linked genes PRL, DRB3, and DYA by PCR-RFLP analysis. Single-locus analysis of gene-centromere recombination rates were theta cen-DYA = 0.042, theta cen-DRB3 = 0.113, and theta cen-PRL = 0.166. The most likely order is cen-DYA-DRB3-PRL. Analysis of typing data from 3 cows revealed three meiotic divisions consistent with "linkage phase exchange" between DYA and DRB3 or PRL. One of the three linkage phase exchanges was confirmed by complementary genotypes in a matched secondary oocyte-first polar body pair. Such linkage phase exchanges could result from four-strand double crossovers between homologous chromosomes. Because all four gametes produced by four-strand double crossovers will be recombinant, more frequent occurrence of such events in females may explain the sexual dimorphism in genetic maps. Alternatively, four-strand crossovers could represent a type of recombination hotspot between DYA and DRB3, suggesting a mechanism for the high recombination frequency (15%) between these two class II genes of the bovine major histocompatibility complex.

Animals↗

PubMed1995

A model of chiasma reduction of closely formed crossovers.

A model of chiasma reduction is developed, evaluated by computer simulation and discussed in relation to the evolution of interference. The model assumes that adjacently formed crossovers can interact, if there is incomplete sister chromatid cohesion between them, and give rise to a reduced number of chiasmata. In the absence of crossover position interference this leads to a considerable risk of non-disjunction for an average sized chromosome. It is suggested that an important function of crossover interference is to reduce this effect. The question is raised whether chiasma reduction takes place today. Some available cytological data can be interpreted as showing that chiasma reduction occurs in normal meiosis. The possibility of chiasma reduction therefore needs further attention.

Animals↗

PubMed1996

Changes in locations of crossover sites over time in de novo generated RNA recombinants.

Recombinant RNAs generated in plants 3 weeks postinoculation with turnip crinkle virus (TCV) genomic RNA and an associated satellite RNA, sat-RNA D, have a majority of TCV crossover sites in a 24-nucleotide repeat (motif IIIA/IIIB) that forms part of a stable hairpin (Carpenter et al., 1995, J. Mol.Biol. 245, 608-622). To determine if parameters other than nucleotide sequence in the crossover region affect junction site selection, recombinants were assayed at various times postinoculation of plants and protoplasts. Populations of recombinants became progressively shorter in plants and larger in protoplasts. Levels of inoculated transcript and age of the plant were not substantial factors in the shifts in crossover site locations. The two most commonly cloned recombinant species were not amplified to detectable levels in protoplasts, suggesting that these molecules are not viable templates for replication. These results suggest that recombination between sat-RNA D and TCV is a very frequent event, and populations of recombinants are likely generated de novo in each infected cell and represent the original recombinant molecules rather than progeny of such molecules. Therefore, factors other than simple selection for recombinants that are more fit to replicate are probably responsible for the differences in junction sites in populations of sat-RNA D/TCV recombinants.

Binding Sites↗

PubMed1992

Identification of crossovers in Wilson disease families as reference points for a genetic localization of the gene.

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. A minimum recombinant analysis using D13S22, ESD, RB1, D13S31, D13S55, D13S26, D13S39, and D13S12, all localized at 13q14-q22, has been carried out in 20 WD families of Northwest-European origin. No inconsistencies have been observed with respect to locus order or location of the WD locus (WND) compared with previous linkage studies. D13S31 was mapped as the closest marker proximal to WND, whereas D13S55 and D13S26 were mapped as the closest markers distal to WND. We have identified a crossover between WND and D13S31 in one family and a crossover between WND and D13S55 in another. These crossover sites can be used as reference points for new chromosome 13q14-q21 markers, and are therefore important for a more accurate mapping of the WD locus.

Chromosome Mapping↗

PubMed1988

Crossover regions in foot-and-mouth disease virus (FMDV) recombinants correspond to regions of high local secondary structure.

The RNA genome of foot-and-mouth disease virus (FMDV) was analysed for the degree of inverted complementarity and thus potential secondary structure using the procedure of Pustell and Kafatos [Nucleic Acids Res (1982) 10: 4765-4782]. Regions of crossover in 42 FMDV recombinants [King et al. (1985) Virus Res 3: 373-384; Saunders et al. (1985) J Virol 56: 921-929] and regions lacking crossovers were assigned an average secondary structure score against which the number of observed recombinants was plotted. In general it was found that the mean value of potential secondary structure is significantly higher in crossover zones than in recombination-free zones. Recombination increased much more steeply with increasing secondary structure in the part of the genome coding for non-structural proteins than in the 5' third of the genome coding for structural proteins.

Aphthovirus↗

PubMed2006

[Questionnaire on crossover renal transplantations in Germany].

Due to increasingly better long-term survival rates with dialysis the number of patients with renal failure constantly increases by 4% annually worldwide. Despite great progress in operative and perioperative management as well as improved immunosuppressive drugs, kidney transplantation still faces two major problems. First of all there is a huge deficit of donor organs and secondly the long-term results of the kidney grafts must be improved. One way to relieve this tense situation may be live kidney donation. In many countries not participating in Eurotransplant, especially the United States and Scandinavia, live kidney donation is performed more often than kidney transplantation from deceased donors. Germany implemented a transplantation law in December 1997. This law also regulates living donation, with exclusion of crossover transplantations. Cross-over transplantation is a special variation of live donation for couples who cannot donate/receive in their respective couple constellation. Therefore, the donor of the one couple donates his/her kidney to the recipient of the other couple and vice versa. According to German legislation this is illegal. We performed a study in order to evaluate the opinions of the German kidney transplant centers on crossover kidney transplantations. The majority of the German transplantation centers believe that crossover transplantation is acceptable with regard to ethical and medical concerns. To enable this kind of kidney transplantation the transplantation law would have to be changed. Nevertheless, nationwide polls show that live kidney donation represents only a very small portion of all transplantations taking place. Live kidney donation should be granted higher priority as dialysis triggers psychological and physical damage, especially in children. For many patients live kidney donation is the only chance for early transplantation with an excellent long-lasting kidney graft function.

Attitude of Health Personnel↗

PubMed2005

A crossover study on lipid and weight changes associated with olanzapine and risperidone.

RATIONALE: The results from case-control and retrospective studies revealed that olanzapine might be associated with more increased risks of metabolic dysfunction than risperidone. The crossover design can minimize the influence of individual variation in metabolic profiles and demographic variables, such as age, sex, concomitant medication use and personal life styles. OBJECTIVES: We design a crossover study to evaluate the metabolic effect of olanzapine and risperidone. METHODS: Fifteen schizophrenic patients were shifted from olanzapine and risperidone or from risperidone and olanzapine due to poor treatment response. The body weights, lipid profiles and fasting glucose levels were assessed before medication switch and 3 months after crossover. RESULTS: In the seven patients taking risperidone at the time of inclusion (risperidone-first group), after shifting to olanzapine, there was a significant increase in triglyceride level (p=0.048) and body weight (p=0.008). In the other eight patients (olanzapine-first group), after shift to risperidone, there was a decrease in triglyceride level (p=0.009), body weight (p=0.049) and body mass index (BMI; p=0.04). When comparing the metabolic profiles in all patients after olanzapine and after risperidone (irrespective of the order of treatment), the mean triglyceride level (p=0.001), body weight (p=0.001) and BMI (p=0.015) were significantly higher in patients receiving olanzapine than in those receiving risperidone. Furthermore, there was a small increase in total cholesterol level (p=0.091) and a small decrease in high-density lipoprotein (HDL) level (p=0.061) in olanzapine group, but the differences did not reach a significant level. There was no significant difference between olanzapine and risperidone in fasting glucose and low-density lipoprotein (LDL). CONCLUSIONS: This study confirms that elevated levels of triglyceride and body weight could be associated with the use of olanzapine as compared with risperidone. The changes in body weights and lipid profiles should be closely monitored in patients during treatment with atypical antipsychotic drugs.

Adult↗

PubMed2002

Patency of superficial femoral vein employed as a crossover femoral artery bypass conduit.

This study assesses the patency of superficial femoral vein used as a crossover femoral artery bypass conduit in patients presenting either with localized groin sepsis, generalized sepsis or in patients with occluded or heavily diseased superficial femoral artery outflow. Twenty patients were followed prospectively with femoral crossover grafts constructed of superficial femoral vein. Twelve patients presented with sepsis and 8 with chronic ischemia from iliac artery occlusion and severely diseased superficial femoral artery outflow. Graft patency was assessed with regular duplex ultrasound examination. There was one perioperative death. Six patients died during the follow-up period. Mean follow-up time was 24.3 months. No graft occluded or required revision. There was no limb loss, graft infection, or graft hemorrhage. Superficial femoral vein offers an effective femoral crossover bypass graft in patients with either localized/generalized sepsis or disadvantaged outflow tracts.

Adult↗

PubMed1995

Three-period crossover trial with ambulatory blood pressure monitoring for evaluating antihypertensive therapy.

A double-blind, three-period, crossover trial used 24-hour ambulatory blood pressure monitoring to compare diltiazem controlled diffusion (CD) 300 mg with placebo. Patients with hypertension (N = 43) were randomly assigned to one of four crossover treatment sequences of three treatment periods each. Ambulatory blood pressure was obtained at the end of each 4-week treatment period. Diltiazem CD significantly decreased diastolic and systolic blood pressure at bihourly ambulatory blood pressure evaluations (p < 0.05, all). However, when all ambulatory blood pressure monitoring data were combined into one statistical model, blood pressure reductions were quantifiably similar to those in the overall bihourly analysis, but with a consistent 24-hour antihypertensive effect for both diastolic and systolic blood pressure relative to that with placebo (i.e., parallel blood pressure profiles) and with increased precision. Mean +/- SE changes in diastolic and systolic blood pressure across the 24-hour dosing interval were -5.6 +/- 0.4 mm Hg and -7.6 +/- 0.5 mm Hg, respectively (p < 0.001, both). Therefore, by using a crossover design with ambulatory blood pressure monitoring, we showed diltiazem CD to reduce blood pressure consistently throughout a 24-hour dosing interval in comparison with placebo in patients with hypertension.

Adult↗

PubMed1995

Fetal acoustic stimulation, an adjunct to external cephalic version: a blinded, randomized crossover study.

OBJECTIVE: Our purpose was to determine whether fetal acoustic stimulation can improve the chance of successful external cephalic version in patients at 36 to 38 weeks' gestation with fetal midline spine position. STUDY DESIGN: A randomized, blinded crossover trial was performed. In this "N of 1" study, the patient served as her own control. RESULTS: Twenty-six patients were enrolled in the study, and three were excluded due to engagement of the fetal breech. In the initial trial with fetal acoustic stimulation to the maternal abdomen, 12 of 12 (100%) changed position to spine lateral and 11 of 12 (92%) were successfully verted. In the control group (fetal acoustic stimulation to nurse's arm), none of 11 (0%) changed position to spine lateral and one of 11 (9%) were successfully verted (p < 0.0001). In the crossover trial eight of 10 (80%) of the original placebo (control) patients were successfully verted after fetal acoustic stimulation to the maternal abdomen and none of 1 (0%) from the original treatment group were successfully verted after placebo fetal acoustic stimulation (p < 0.0001). Combined data from the original and crossover trials indicates 19 of 22 (86%) successful versions after fetal acoustic stimulation to maternal abdomen compared with one of 12 (8%) that had successful external cephalic version after placebo fetal acoustic stimulation. CONCLUSION: Fetal acoustic stimulation shifts fetal position to spine lateral, which increases successful version of fetuses with midline fetal spine presentations.

Acoustic Stimulation↗

PubMed1983

Recombination in adenovirus: DNA sequence analysis of crossover sites in intertypic recombinants.

The nucleotide sequence of the adenovirus type 5 genome has been determined for a 620-bp region that spans the C terminus of the pVI gene and the N terminus of the hexon gene, and compared to the adenovirus type 2 DNA sequence: 25 base changes have been identified, most of which do not lead to alterations in the amino acid sequence and regulatory signals in the region. Crossover sites in three intertypic recombinants have been previously located in this region of the genome by fine restriction mapping. A sequence determination for the three recombinants, and the four ts mutants used in generating the ts+ recombinants, was carried out. The crossovers were in each case located in a small region of complete sequence homology (from 45 to 156 nucleotides long) flanked on either side by sequences derived from each parent. These structures are compatible with a reciprocal crossing over model of generalised recombination, where a recombinant joint has resolved in a region of high DNA homology. For the recombinants considered here, this region abutts onto a neighbouring region of much lower sequence homology, and it is possible that the position of the crossover is determined at least in part by the termination of branch migration at a heterologous boundary.

Adenoviruses, Human↗

PubMed1986

The primary structure of crossover regions of intertypic poliovirus recombinants: a model of recombination between RNA genomes.

The nucleotide sequence of crossover sites in the genome of four intertypic (type 3/type 1) poliovirus recombinants has been determined. The approximate boundaries of the crossover regions were first estimated by RNase T1 oligonucleotide mapping of the recombinant genomes; then appropriate regions were sequenced by the chain termination method using oligonucleotide-primed reverse transcription of the recombinant RNAs. The crossover sites (defined as the contiguous sequences shared by the recombinant and both parental genomes flanked, in the recombinant genome, by heterotypic RNA segments) are 5, 5, 7, and 11 nucleotides long, respectively. The recombination was precise and was not accompanied by any other genetic alterations. The recombination sites were found to be located within genome segments having a potential to form secondary structure elements. Based on this observation, a model of recombination between picornaviral RNA genomes has been proposed. The essence of this model consists in bringing together homologous regions of two recombining RNA genomes via formation of intermolecular duplexes, detachment of the nascent 3' end of the newly synthesized complementary RNA from a "parting" site on the first template and its subsequent "jumping" to the identical (or closely related) "anchoring" site on the other template. Features of this model are discussed in some detail.

Base Sequence↗

PubMed1986

Localized conversion at the crossover sequences in the site-specific DNA inversion system of bacteriophage P1.

The crossover sites for site-specific C inversion consist of imperfect 12 bp inverted repeats with the dinucleotide TT at the center of symmetry. The phage P1 Cin recombinase acts not only at these cix sites but also less efficiently at cix-related sequences called quasi-cix sites, cixQ. When cixQ contains a central dinucleotide TT, crossover occurs in vivo at the 2 bp sequence TT in the normal and the quasi-cix sites. If cixQ carries only one T residue, inversion-associated localized conversion can occur at the mismatched position within the 2 bp sequence. The results indicate that Cin generates 2 bp staggered cuts in vivo and that reciprocal strand exchanges occur at these 2 bp crossover sequences.

Chromosome Inversion↗

PubMed1983

Reaction-time crossover in psychiatric outpatients.

Simple reaction time (SRT) was measured in schizophrenic, bipolar affective disorder, and never-psychotic outpatients to determine the specificity of SRT crossover to schizophrenia. A crossover pattern like that reported in other studies was found among the schizophrenics, but the average curve was not different from that of the other groups. Schizophrenics tended to have higher rates of crossover at the 7-second preparatory interval (47% vs. 17%-28%) but not substantially so. These data question the specificity of this behavioral trait to schizophrenics.

Adult↗

PubMed1990

The effect of therapeutic treatment crossovers on the power of clinical trials. The Silicone Study Group.

The Silicone Study is a randomized clinical trial comparing two surgical methods for reattaching the retina when detachment is associated with proliferative vitreoretinopathy. If the retina redetaches subsequently, the patient will usually undergo additional surgery using the assigned treatment. In a limited number of cases the patient may be switched to the alternative treatment, if a "therapeutic crossover" is endorsed by an independent committee of ophthalmologists. A successful outcome is continued anatomic attachment of the retina and an adequate visual result 6 months after the final surgery. The therapeutic treatment crossovers affect the power of the trial to detect a difference between the two treatments. A simulation study shows that the loss in power depends on the magnitude and degree of bias in the probability of being switched from one treatment to the other. Unlike the usual case of lack of compliance, complete information about treatment history may allow statistical adjustment for the crossover. The outcome may be modeled using a multinomial distribution. Much of the power lost due to switching may be recouped under some strong assumptions.

Computer Simulation↗

PubMed2005

Application of case-crossover and case-time-control study designs in analyses of time-varying predictors of T-cell homeostasis failure.

PURPOSE: To evaluate the association of sexual behavior and recreational drug exposures with T-cell homeostasis failure (TCHF), which corresponds to the onset of a rapid decline in an individual's T lymphocyte count, which occurs on average approximately 1.75 years prior to an initial diagnosis of acquired immunodeficiency syndrome (AIDS). METHODS: A case-crossover design and a case-time-control design, both nested within the Multicenter AIDS Cohort Study of 4954 homosexual and bisexual men initiated in 1983. RESULTS: In the case-crossover analysis, use of both recreational drugs and hashish were found to be protective against TCHF (odds ratios < or = 0.41), based on comparisons with four earlier control periods. However, a significant decreasing trend in the prevalence of these exposures was observed over time, thus motivating the implementation of the case-time-control design. Using the latter approach, the associations of drug use (odds ratio=0.53; 95% confidence interval (CI): 0.22, 1.28) and hashish use (odds ratio=0.46; 95% CI: 0.20, 1.05) with TCHF were no longer statistically significant. CONCLUSIONS: The difference in inferences between these approaches demonstrates the importance of evaluating temporal trends in exposures when using a case-crossover design.

Acquired Immunodeficiency Syndrome↗

PubMed2006

Cluster-crossover design: a method for limiting clusters level effect in community-intervention studies.

The cluster-crossover design can be used for clinical trials comparing two or more interventions in a naturally formed study population, i.e. a cluster. This design differs from that of a crossover study, in that the treatment sequence is allocated at the cluster level. A cluster-crossover study can thus be considered as a cluster-randomized controlled study with additional periodic cluster-randomization(s) or treatment permutation(s) during the study. The data must be analyzed with hierarchical models with random effects in order to allow for different outcome probabilities in each period, cluster and cluster-period. Original data from two published field studies of hospital infection control based on this design are used here to illustrate the impact of different statistical models on the interpretation of the results.

Clinical Trials as Topic↗

PubMed2026

An expanded breakfast buffet increases daily energy and protein intakes in hospitalised patients: A prospective crossover quality improvement study.

BACKGROUND & AIMS: Inadequate dietary intake remains common during hospitalisation. Ordinary hospital meals are central to nutritional intake, but their contribution depends on what is offered and what patients are able and willing to eat. We evaluated whether a preference-informed, limited expansion of the hospital breakfast buffet could increase total daily energy and protein intakes. METHODS: This prospectively structured, ward-based crossover quality-improvement study was conducted in seven inpatient wards at a tertiary university hospital. Each ward was observed for four consecutive days and randomly allocated to begin with standard or expanded breakfast, after which conditions alternated daily. The expanded buffet consisted of standard breakfast supplemented with familiar energy- and protein-rich foods selected from previous patient-choice data. Twenty-four-hour intake was registered using component-level weighed food records during the day and nursing registration overnight. Primary outcomes were total daily energy and protein intakes. Linear mixed-effects models adjusted for observation day and ward-level starting sequence and accounted for repeated patient observations and ward-level clustering. Analyses used data from patients who consumed breakfast and contributed analysable observations under both breakfast conditions. RESULTS: The primary crossover population included 71 patients contributing 188 analysable patient-days. Compared with standard breakfast, the expanded breakfast increased total daily energy intake by +198 kcal/day (95% CI 44 to 352) and protein intake by +6.8 g/day (95% CI 1.0 to 12.5), without a statistically significant increase in total food weight. Daily energy and protein adequacy increased by +8.7 and + 6.8 percentage points, respectively. The increase was driven mainly by breakfast intake, with no measurable reduction in non-breakfast intake. CONCLUSIONS: A limited expansion of the ordinary hospital breakfast buffet increased total daily energy and protein intakes in the primary crossover population of hospitalised adults who consumed breakfast. This increase occurred without a statistically significant increase in total food weight or a measurable reduction in non-breakfast intake. Small, preference-informed additions of familiar energy- and protein-rich foods at breakfast may improve daily intake by increasing the nutrient yield of foods patients are able or willing to eat.

Humans↗