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PubMed1988

Analysis of crossover type in the alpha -3.7 haplotype among sickle cell anemia patients from various parts of Africa.

The frequency of alpha+-thalassemia has been determined in African populations carrying beta S-chromosomes of different origins. All these alpha+ thalassemias result from a right-ward deletion. Restriction mapping of the alpha -3.7/haplotype with the enzyme ApaI only showed the presence of a type I crossover. RsaI polymorphism at the 5' end of Z alpha 2 is largely represented in the normal population (gene frequency 23%) but, in our series, never associated with the alpha -3.7/haplotype.

Africa↗
PubMed2006

Meiotic recombination hotspots in plants.

Many studies have demonstrated that the distribution of meiotic crossover events along chromosomes is non-random in plants and other species with sexual reproduction. Large differences in recombination frequencies appear at several scales. On a large scale, regions of high and low rates of crossover have been found to alternate along the chromosomes in all plant species studied. High crossover rates have been reported to be correlated with several chromosome features (e.g. gene density and distance to the centromeres). However, most of these correlations cannot be extended to all plant species. Only a few plant species have been studied on a finer scale. Hotspots of meiotic recombination (i.e. DNA fragments of a few kilobases in length with a higher rate of recombination than the surrounding DNA) have been identified in maize and rice. Most of these hotspots are intragenic. In Arabidopsis thaliana, we have identified several DNA fragments (less than 5 kb in size) with genetic recombination rates at least 5 times higher than the whole-chromosome average [4.6 cM (centimorgan)/Mb], which are therefore probable hotspots for meiotic recombination. Most crossover breakpoints lie in intergenic or non-coding regions. Major efforts should be devoted to characterizing meiotic recombination at the molecular level, which should help to clarify the role of this process in genome evolution.

Animals↗
PubMed1999

The effect of four different antihypertensive medications on cardiovascular regulation in hypertensive sleep apneic patients--assessment by spectral analysis of heart rate and blood pressure variability.

OBJECTIVE: To study the effect of antihypertensive medications on autonomic nervous system in patients with hypertension and sleep apnea syndrome using frequency domain measures of heart rate and blood pressure variabilities. METHODS: The beta-receptor blocking agent atenolol (50 mg), the calcium antagonist isradipine SRO (2.5 mg), the diuretic hydrochlorothiazide (25 mg) and the ACE inhibitor spirapril (6 mg) once daily were given in a double-blind crossover schedule for 8 weeks. Cardiovascular autonomic control was assessed using frequency domain measures of heart rate variability during the spontaneous and controlled breathing tests. During orthostatic maneuver and cold pressor test the blood pressure variability analysis also was performed. RESULTS: In general, the responses of heart rate and blood pressure variabilities were abnormal in the patients with arterial hypertension and sleep apnea syndrome compared to reference data. Of the four drugs, only atenolol effected heart rate and blood pressure variabilities as it shifted the autonomic regulation to the vagal direction. Other antihypertensive drugs did not change any parameter of heart rate or blood pressure variabilities. CONCLUSION: The short-term treatment with atenolol in patients with arterial hypertension and sleep apnea syndrome is associated with normalization of autonomic nervous control judged by heart rate and blood pressure variability. Thus, beta-receptor blockade may have adjunctive beneficial effects beyond blood pressure reduction in these patients. However, the long-term effects of blood pressure reduction on autonomic nervous control remain to be studied.

Adrenergic beta-Antagonists↗
PubMed1978

The effects of one-day treatment of anxiety with high doses of halazepam.

The main purposes of this study were to examine the effects of one-day treatment of anxiety and to test whether significant relief of anxiety can be achieved in a short time period by frequency individual adjustment of doses. A double-blind crossover study of halazepam and placebo was carried out with 22 patients, 20 completing the study. Each treatment lasted for one day. Oral medication was administered starting with a dose of 40 mg and the dose adjusted every 2 hours. The total daily dose did not exceed 600 mg. Several rating and self-rating scales were used. All observer rating scales and several self-rating scales discriminated at a significant level. The design appeart to be suitable for the rapid screening for anti-anxiety properties of new drugs.

Adult↗
PubMed1982

Verapamil therapy for stable exertional angina pectoris.

Clinical and exercise responses to therapy with the calcium-channel blocking agent verapamil were assessed in 26 patients with stable exertional angina pectoris using a double-blind, placebo-controlled, randomized crossover study design. Verapamil, 480 mg daily, reduced the frequency of angina attacks (5.6 +/- 7.3 to 2.2 +/- 3.0 attacks per week, p less than 0.001) and number of nitroglycerin tablets consumed (3.4 +/- 4.9 to 1.2 +/- 2.5 tablets per week, p less than 0.05), and increased exercise duration (6.4 +/- 2.1 to 7.5 to 1.8 minutes, p less than 0.001) (all data are mean +/- standard deviation). These changes were significantly better than those seen with placebo. These beneficial effects of verapamil were related to significant reduction in the heart rate-systolic blood pressure product during submaximal exercise. Adverse effects from verapamil were few and consisted primarily of constipation in 6 patients. A total of 193 patients had been entered in 6 independent clinical trials, which have compared verapamil with placebo for the treatment of stable exertional angina pectoris, using a similar study design. The combined evidence from all these studies indicates that verapamil is a highly effective and safe drug for the treatment of stable effort-related angina pectoris.

Adult↗
PubMed1999

Effects of short-acting and long-acting loop diuretics on heart rate variability in patients with chronic compensated congestive heart failure.

BACKGROUND: We investigated the effects of a short-acting loop diuretic (furosemide) and a long-acting loop diuretic (azosemide) on heart rate variability, fluid balance, and neurohormonal responses in patients with mild to moderate chronic congestive heart failure. METHODS: Nineteen patients with mild to moderate chronic congestive heart failure received furosemide (40 to 60 mg/day) or azosemide (60 to 90 mg/day) for 5 days in a crossover manner. We performed time-domain and frequency-domain analyses of 24-hour Holter electrocardiographic recordings to assess heart rate variability. RESULTS: The 24-hour urinary sodium excretion was similar during the furosemide and azosemide treatment periods but was significantly greater in the first 2 hours after drug administration during furosemide treatment. Plasma renin activity and the hematocrit level increased and high-frequency power significantly decreased 2 hours after the administration of furosemide only. The standard deviation of all normal R-R intervals and the root mean square of successive differences in the R-R interval were lower with furosemide than with azosemide (P <.05). CONCLUSIONS: Furosemide, a short-acting loop diuretic, has a greater influence on heart rate variability and fluid balance than azosemide, a long-acting loop diuretic, in patients with mild to moderate chronic congestive heart failure.

Blood Pressure↗
PubMed1983

Nifedipine in chronic stable angina: a double-blind placebo-controlled crossover trial.

Thirty patients with chronic stable angina pectoris were randomized in a double-blind prospective placebo-controlled crossover trial to assess the efficacy of nifedipine (30 to 60 mg/day orally) in controlling symptoms and objective signs of myocardial ischemia using a symptom-limited treadmill exercise test. Adverse effects that occurred during both nifedipine and placebo treatment were minor and generally well tolerated. Twenty-three patients were analyzed from the crossover phase of the study. Nifedipine significantly reduced the frequency of angina by 55% and nitroglycerin consumption by 59%, and increased exercise time by 34%. These changes were significantly greater than those in the placebo group. Hemodynamic evaluation during exercise revealed a significant reduction in systolic and diastolic blood pressures in the nifedipine group at the onset of angina and at maximal exercise without significant differences in heart rate responses in the nifedipine and placebo groups. The pressure-rate product during submaximal exercise was significantly smaller in the nifedipine group than in the placebo group, but did not differ significantly in the 2 groups at the onset of angina or on maximal exercise. Furthermore, S-T segment depressions that occurred during exercise at the same pressure-rate products were smaller in the nifedipine period than in the placebo period. Thus, it appears that the antianginal effects of nifedipine are caused by a reduced myocardial oxygen demand for a specific work load and possibly by an increased blood supply to ischemic myocardium.

Adult↗
PubMed1984

Techniques for manipulating chromosomal rearrangements and their application to Drosophila melanogaster. II. Translocations.

Translocations have long been valued for their segregational properties. This paper extends the utility of translocations by considering recombinational derivatives of pairs of simple reciprocal translocations. Three major derivative structures are noted. One of these derivatives is suitable for use in half-tetrad experiments. A second should find use in recombining markers with translocation breakpoints. The third is an insertional-tandem duplication: it has a section of one chromosome inserted into a heterologue with a section of the latter chromosome tandemly repeated about the breaks of the insert. All of these structures are contained in "constellations" of chromosomes that regularly segregate aneuploid-1 products (informationally equivalent to nonrecombinant adjacent-1 segregants) for one of the parental translocations but do not segregate euploid products. This is in contrast to the parental T1/T2 constellations which segregate euploid products but not aneuploid-1 products. Methods are described for selecting translocation recombinants on the basis of this dichotomy. Several examples of translocation recombinants have been recovered with these techniques, and the recombination frequencies seem to be consistent with those observed for crossovers between inversion breakpoints. Recombinant chromosomes tend to disjoin, but it is observed that the tendency may vary according to the region involved in the recombination, and it is suggested that this difference reflects a difference in chiasmata terminalization times. Special consideration is given to insertional-tandem duplications. Large insertional-tandem duplications are useful in gene dosage studies and other experiments that require an insert from one chromosome to another. Large duplications can be deleted to form small duplications. To generate a small insert for a specified region, it is only necessary to have one translocation with a breakpoint flanking the region of interest. The second translocation can have a breakpoint quite far from the region: an insertional-tandem duplication containing the region that has one closely flanking breakpoint can be deleted to create a smaller duplication that has two closely flanking breakpoints.

Aneuploidy↗
PubMed1975

Mapping and gene conversion studies with the structural gene for iso-1-cytochrome C in yeast.

We have investigated the order of the four genes cyc1, rad7, SUP4, and cdc8 which form a tightly linked cluster on the right arm of chromosome X in the yeast Saccharomyces cerevisiae. Crossing over and coconversion data from tetrad analysis established the gene order to be centromere-cyc1-rad7-SUP4. Also cdc8 appeared to be distal to SUP4 on the basis of crossovers that were associated with conversion of SUP4. The frequencies of recombination and the occurrence of coconversions suggest that these four genes are contiguous or at least nearly so. Gene-conversion frequencies for several cyc1 alleles were studied, including cyc1-1, a deletion of the whole gene that extends into the rad7 locus. The cyc1-1 deletion was found to be capable of conversion, though at a frequency some fivefold less than the other alleles studied, and both 3:1 and 1:3 events were detected. In general 1:3 and 3:1 conversion events were equally frequent at all loci studied, and approximately 50% of conversions were accompanied by reciprocal recombination for flanking markers. The orientation of the cyc1 gene could not be clearly deduced from the behavior of the distal marker SUP4 in wild-type recombinants that arose from diploids heteroallelic for cyc1 mutations.

Chromosome Mapping↗
PubMed2005

Polaronic and nonadiabatic phase diagram from anomalous isotope effects.

Isotope effects (IEs) are powerful tools to probe directly the dependence of many physical properties on lattice dynamics. In this Letter we investigate the onset of anomalous IEs in the spinless Holstein model by employing the dynamical mean field theory. We show that the isotope coefficients of the electron effective mass and of the dressed phonon frequency are sizable also far away from the polaronic crossover and mark the importance of nonadiabatic lattice fluctuations. We draw a nonadiabatic phase diagram in which we identify a novel crossover, not related to polaronic features, where the IEs attain their largest anomalies.

Journal Article↗
PubMed2001

Development of a gene cloning and inactivation system for halorespiring Desulfitobacterium dehalogenans.

Efficient host-vector systems have been developed for the versatile, strictly anaerobic, halo- and fumarate-respiring gram-positive bacterium Desulfitobacterium dehalogenans. An electroporation-based transformation procedure resulting in approximately 10(3) to 10(4) transformants per microg of the cloning vector pIL253 was developed and validated. The broad-host-range vector pG+host9 was shown to replicate at a permissive temperature of 30 degrees C, whereas the replicon was not functional at 40 degrees C. The D. dehalogenans frdCAB operon, predicted to encode a fumarate reductase, was cloned, characterized, and targeted for insertional inactivation by pG+host9 carrying a 0.6-kb internal frdA fragment. Single-crossover integration at the frdA locus occurred at a frequency of 3.3 x 10(-4) per cell and resulted in partially impaired fumarate reductase activity. The gene cloning and inactivation systems described here provide a solid basis for the further elucidation of the halorespiratory network in D. dehalogenans and allow for its further exploitation as a dedicated degrader.

Anaerobiosis↗
PubMed1997

A new Thermus-Escherichia coli shuttle integration vector system.

We established a Thermus thermophilus strain in which the pyrE gene (coding for orotate phosphoribosyltransferase of the pyrimidine biosynthetic pathway) was totally deleted. We also constructed an integration vector, which consisted of the Escherichia coli plasmid vector pBluescript and a 2.1-kb segment of the T. thermophilus leu operon sequence, for the integration of a foreign gene into a chromosome of the thermophile. pyrE and leuB genes were used as probes to test the integration vector. The integration vector pINV, bearing the pyrE gene, transformed the delta pyrE strain at a frequency of 6 x 10(-5) through a single crossover event. The leuB gene could also be used as another marker of the integration vector system. The vector could be integrated at the expected site. By digesting the chromosomal DNA of the T. thermophilus transformants with a unique restriction enzyme, the vector could be recovered into E. coli after the recircularization in vitro. The kanamycin nucleotidyltransferase gene could be successfully expressed in the thermophile by using pINV.

3-Isopropylmalate Dehydrogenase↗
PubMed1989

High-level recombination specific to polyomavirus genomes targeted to the integration-transformation pathway.

An unusually high incidence of interviral recombination was found in the process of integration of the polyomavirus genome concomitant with neoplastic transformation of nonpermissive cells. Transformants were isolated after mixed infections of Fischer rat cells with two mutants lacking restriction endonuclease sites and were analyzed for the presence of unselected integrated recombinant restriction fragments. A large fraction of the transformants isolated (38% of the 64 transformed cell lines studied) contained recombinant viral genomes that had undergone recombination in a 1.3-, 1.7-, or 3.6-kilobase-pair interval. More than 90% of these recombinant transformants showed evidence of crossovers in multiple intervals. To our knowledge, the recombination frequencies observed in these experiments represent the highest frequencies of homologous recombination reported for a mitotic mammalian system that does not involve transfection. In contrast to the elevated level of recombination in the integrated viral genomes, no evidence of recombination was obtained among the replicated unintegrated pool of viral genomes isolated from the same population of infected cells from which the recombinant transformants were derived. Either of two hypotheses can provide an explanation for the segregated recombination: either recombination occurs at elevated levels in a small, recombination-prone fraction of the population destined to become transformed, or recombination occurs only among those viral genomes which are engaged in the process of integration and thus interact with a recombinogenic host machinery (for example, the host scaffold). We favor the latter hypothesis.

Animals↗
PubMed1976

Effect of propranolol on acute withdrawal tremor in alcoholic patients.

The effect of the beta-adrenergic blocking agent propranolol was tested on positional tremor occurring during acute alcohol withdrawal using a double-blind crossover method and electrical recording of tremor amplitude and frequency. The difference between the effects of propranolol and placebo was not significant.

Acute Disease↗
PubMed1976

Objective evaluation of antitussive agents under clinical conditions.

A new method for objective assessment of cough under normal or pathological conditions is described. Thoracic coughing can be discriminated from any other pressure wave because of its relatively high frequency. This method was applied in a double blind crossover trial in 18 patients with respiratory disease.

Antitussive Agents↗
PubMed1981

Effect of domperidone on the motility of antrum, pylorus and duodenum in man.

Domperidone stimulates esophageal motility and increases gastric emptying rates. In the present study the effect of 8 mg domperidone i.v. on antroduodenal motility was investigated double blind and crossover in 10 healthy subjects. Domperidone increased significantly the frequency, amplitude and duration of duodenal and the duration of antral contractions (p less than 0.05). Pyloric motility was not affected. It is concluded that the stimulatory effect of domperidone on antroduodenal motility may contribute to the beneficial effect of the drug in gastroesophageal reflux and gastric ulcer.

Adult↗
PubMed1994

[Food habits among children in a district of the island of Gran Canaria].

OBJECTIVE: To find out the characteristics of the diet of a population-group of young children and to quantify their caloric and nutrient intake. DESIGN: A descriptive study of a crossover type by means of a questionnaire on the frequency of food consumption. Stratified random sampling. SETTING: A Primary Care Centre. PATIENTS AND OTHER PARTICIPANTS: 264 healthy children aged from 2 to 8, representative of a District. MEASUREMENTS AND MAIN RESULTS: The children studied had overall sufficient caloric intake ("calories consumed/calories recommended" index of 1 +/- 0.2), with an excess of proteins (16.6 +/- 1.8% of calories) and lipids (36.3 +/- 4% of calories, mainly of animal origin) to the detriment of carbohydrate intake (47.7 +/- 5% of the caloric intake). There was an important percentage (42%) of children whose iron intake was deficient. Only 9% of children had a poor calcium intake. The vitamin intake was adequate. CONCLUSIONS: The variability of alimentary customs between zones means that we must identify the dietetic habits of the population group (or even individuals) we are serving, especially for the paediatric age group. We propose systematic Primary Care use of questionnaires on food consumption to enable the detection and correction of nutritional dangers.

Child↗
PubMed1998

[Dependence on self-care and walking of the aged in a rural community].

OBJECTIVE: To evaluate the dependence on 5 basic daily activities (BDA) and on walking, and their relationship to the frequency of attendance at the family doctor. DESIGN: A crossover study using a home survey of health. SETTING: Town of Villanueva de los Castillejos in Huelva. PARTICIPANTS: Those 65 or over. INTERVENTIONS: The dichotomous form of the Katz Index, with the incontinence item excluded (scores from 0-5), was used. Walking was assessed by the Functional Walking Categories (FWC) of Massachusetts General Hospital. RESULTS: Information on 139 men and 231 women was obtained (85.6% of the actual population). 15.3% (95% CI, 11.3-19.0), 12.4% of the men and 16.9% of the women (p > 0.05), stated their dependence in one or more BDA. 22.5% of the population (95% CI, 18.2-26.8), 8.9% of the men and 30.6% (p = 0.001) of the women, said they found it difficult to walk. CONCLUSIONS: There is a high rate of dependence in the population group. Light dependence is associated with more frequent medical consultations than either independence or severe dependence.

Activities of Daily Living↗