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PubMed1990

The Gm-Pi linkage in 843 French families: effect of the alleles Pi Z and Pi S.

Linkage analysis was performed between Gm and Pi in 843 French families. The overall recombination fraction is equal to 0.25 with a sex difference ratio of 1.4 (recombination fraction of 0.20 in males and 0.29 in females), confirming previous results in the literature. Our study does not confirm the existence of a heterogeneity in recombination rate of Pi S versus non-S alleles, but it confirms the previous finding that the presence of the Pi Z allele tends to decrease the recombination rate between the two loci. This decrease appears to be similar in both sexes, and not uniquely in males as previously noted. This result suggests a possible linkage disequilibrium between the Pi Z allele and a presumably large inversion between the two loci Gm and Pi.

Alleles↗
PubMed1991

Genetic similarity maps and immunoglobulin allotypes of eleven populations from the Pyrenees (France).

The genetic heterogeneity of eleven populations from the Pyrenees (France) based on the polymorphism of the immunoglobulin allotypes is studied by means of a 'genetic similarity map'. The method described here, called 'Mobile Node Method', allows the deformation of a square grid, in which the studied region is represented, by moving the nodes at each step in order to reduce the difference between the geographic and genetic distances. This tool allows the overall quantification of the genetic heterogeneity of a population set and possibly the study of its dynamics. Other maps constructed to complete the interpretation are 'map of moving vectors', 'iso-displacement curves' and 'site displacements'. This study identified an overall genetic homogeneity among the Pyrenean populations and several local genetic heterogeneities in different regions.

France↗
PubMed1989

Potentiation by TRH of the effect of antidepressants in the forced-swimming test, involvement of dopaminergic and opioid systems.

1. It has been shown that thyrotropin releasing hormone (TRH) can potentiate the effects of the antidepressant, imipramine, as measured by the mouse forced-swimming test. This potentiation is not associated with an increase of effective levels of noradrenaline in the synaptic clefts, but depends upon the integrity of opioid systems. The present study was designed to investigate: (a) the potentiation by TRH of the effects of other antidepressants, using the same test; (b) the possible involvement of other neuronal systems, such as the 5-hydroxytryptaminergic and dopaminergic systems; (c) the contribution of the opioid and dopaminergic systems to the potentiation of the actions of other antidepressants by TRH. 2. The effects of nortriptyline, amineptine, maprotiline, nomifensine and mianserin, but not that of clomipramine, were potentiated by TRH (2 mg kg-1, i.p.). The inhibitor of 5-hydroxytryptamine synthesis, p-chlorophenylalanine (PCPA), did not prevent the effect induced by imipramine plus TRH. Blockade of dopaminergic systems by gamma-butyrolactone (GBL) (37.5 mg kg-1, i.p.), alpha-methyl-p-tyrosine (AMPT) (125 mg kg-1, i.p.) and apomorphine (0.025 mg kg-1, i.p.) antagonized the effects induced by various antidepressants alone (at high, effective doses) or at lower ineffective doses in association with TRH. The effect induced by imipramine plus TRH was also blocked by sulpiride (16 mg kg-1, i.p.). Pretreatment with the opioid antagonist, naloxone, inhibited the effects induced by nomifensine plus TRH or mianserin plus TRH but not those induced by nortriptyline plus TRH, maprotiline plus TRH or amineptine plus TRH. When high active doses of the antidepressants were used alone, only the clomipramine effect was blocked by naloxone. 3. These data indicate that TRH is able to potentiate the effect not only of imipramine but of other antidepressants in the mouse forced-swimming test, although these other antidepressants act in various ways on cerebral amines. The antagonism of the effects induced by the antidepressants alone or in association with TRH after blockade of dopaminergic systems may indicate a reversal of the effect of the antidepressants by blockade of dopaminergic systems. Hence, the same mechanisms would be involved in the effects induced by antidepressants alone or in association with TRH, with respect to dopaminergic systems. However, different mechanisms of action seem to be responsible for the potentiation of TRH of the effect of the various antidepressants, since the involvement of the opioid systems varies according to the antidepressant tested.

5-Hydroxytryptophan↗
PubMed1992

Protein-energy malnutrition in elderly medical patients.

STUDY OBJECTIVE: To evaluate (1) the prevalence of protein-energy malnutrition in elderly patients; (2) the changes in nutritional status during the hospital stay; and (3) (main objective) the relationship between simple nutritional parameters and short-term in-hospital mortality. DESIGN: Prospective time series at admission and on the 15th day of hospitalization. SETTING: Medical care unit in a teaching hospital. PARTICIPANTS: Consecutive sample of 324 hospitalized patients greater than or equal to 70 years (86.4% of eligible patients). Norms of measurements were obtained from a referred sample of healthy control subjects (26 males and 36 females). MAIN OUTCOME MEASURES: Mid-arm circumference, triceps skinfold thickness, serum albumin, prealbumin, and retinol-binding protein levels were measured in patients at admission and on the 15th day. RESULTS: (1) Prevalence of PEM was 30% in male and 41% in female patients. (2) Both mid-arm circumference and serum albumin level decreased over the first 15 days of hospital stay (53 patients, paired t test, P less than 0.05). Triceps skinfold thickness did not change. (3) A step-wise discriminant-function analysis determined the utility of the parameters at admission as predictors of in-hospital mortality before the 15th day. Mid-arm circumference, triceps skinfold thickness, albumin, and prealbumin levels, as well as age, are predictors of in-hospital mortality, with 73% sensitivity, 69% specificity, and 70% of correctly classified patients of both sexes. CONCLUSIONS: Parameters used are predictors for short-term in-hospital mortality of elderly patients hospitalized in an acute medical unit. The lean body mass is preferentially mobilized for energy during hospitalization.

Aged↗
PubMed1997

Comparison of subcutaneous and intravenous administration of a solution of amino acids in older patients.

OBJECTIVE: To compare the plasma amino acid (AA) concentrations obtained by the infusion of an AA solution (660 mOsm/L, pH 7) using the subcutaneous (SC) with that using the intravenous (i.v.) route in older patients. DESIGN: A prospective, randomized, cross-over study. SETTING: A hospital geriatric ward. PARTICIPANTS: Six patients with a mean age of 84 years. MEASUREMENTS: The infusion of the AA solution (IV or SC) lasted 6 hours. Blood was sampled at 0, 2, 4, 6, 8, 10, 14, 18, and 24 hours from the start of the infusion to determine plasma AA level by the phenyl-isothiocyanate method. RESULTS: Compared with baseline values, plasma AA concentrations increased to a significantly higher level from the second to the tenth hour and from the second to the fourteenth hour during i.v. and SC infusions, respectively. Plasma AA levels did not differ between the two routes. SC infusion was well tolerated. CONCLUSION: Assuming that nutritional sufficiency is the desired result of plasma AA infusion, we conclude the SC route is well tolerated and offers the possibility of nitrogen supplementation for older patients over short periods of time, when oral protein intake is transiently insufficient or impossible, as a way to limit, but not to treat, protein-energy malnutrition.

Aged↗
PubMed1990

Skin acceptance of transcutaneous nitroglycerin patches: a prospective study of 33 patients.

Transdermal nitroglycerin is commonly used and may induce contact dermatitis. The frequency of adverse skin reactions is controversial and may vary from 10% to 75%, according to various authors. 33 patients using transdermal nitroglycerin for more than 7 days were examined and patch tested (nitroglycerin 0.5% aq., 2% pet. and TTS in toto). 5 patients (15%) had adverse reactions. The patch tests were all negative in the 33 patients. Contact dermatitis occurs in many cases, about 15% of the cases with the newly available TTS, and even if patients respect the conditions for using TTS. These contact dermatitides are mainly irritant reactions and do not require transdermal nitroglycerin treatment to be stopped. Nevertheless, since some cases of allergic contact dermatitis have been reported, a contact dermatitis from transdermal nitroglycerin should lead to patch testing.

Administration, Cutaneous↗
PubMed2005

Conventional versus reduced-intensity conditioning regimen for allogeneic stem cell transplantation in patients with hematological malignancies.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) from human leukocyte antigen (HLA)-compatible sibling donors is a potential curative treatment for hematological and non-hematological malignancies. Nevertheless, high mortality rates may be associated with this therapy, especially in older patients, those with other comorbidities or who receive a second HSCT. PATIENTS AND METHODS: We analyzed the factors associated with transplant-related mortality (TRM) and overall survival in 157 consecutive adult patients (104 males and 53 females) who received a HSCT [29 bone marrow (BM) transplantation and 128 peripheral blood (PB) transplantation] from a HLA-identical sibling between January 1995 and March 2002 in our institution. One hundred patients received a standard conditioning prior to HSCT (STAND) and 57 patients received a reduced-intensity conditioning (RIC) HSCT. Fifty-eight patients were in an early phase at transplant and 99 in a non-early phase. Median age was 46 yr (16-66), and 90 patients (57%) were >45 yr of age. RESULTS: Patients in the RIC group were older than those in the STAND group, and had a higher proportion of non-early disease phases including a prior autologous HSCT in 39%. Median follow-up for survivors was 28 and 15 months in the STAND and RIC groups (P < 0,001), respectively. Cumulative incidence of TRM at 2 yr was 30% [95% confidence interval (CI) 22-41%] for the STAND group and 22% (95% CI 13-37%) for the RIC group [non-significant (NS)]. Factors associated with a higher TRM in multivariate analysis were: STAND vs. RIC conditioning regimen [relative risk (RR) 5.4; 95% CI 2.3-12.8; P < 0.001]; age > or =45 yr vs. <45 yr (RR 5; 95% CI 2.4-10.8, P < 0.001); second vs. first HSCT (RR 2.8, 95% CI 1.3-6.3, P = 0.01) and non-T-cell-depleted vs. T-cell-depleted graft (RR 2.7, 95% CI 1.3-5.8, P = 0.009). Overall survival (OS) at 2 yr was 52.5 +/- 10.4% for STAND group and 59 +/- 16.8% in RIC group. Factors associated with poorer OS in multivariate analysis were: STAND vs. RIC conditioning regimen (RR 3.4, 95% CI 1.7-6.9, P = 0.001); age > or =45 vs <45 yr (RR 2.5, 95% CI 1.4-4.5, P = 0.002) and diagnosis [other than chronic myeloid leukemia (CML) vs. CML] (RR 2.6, 95% CI 1.2-5.7 P = 0.02). CONCLUSIONS: Our results indicate that the introduction of RIC allogeneic HSCT for patients at high risk for TRM (advanced age, prior HSCT and non-T-cell depletion) leads to a reduction in the TRM and improvement in the OS.

Adolescent↗
PubMed1980

High frequency of the properdin factor Bf F1 and its linkage to HLA in French Basques.

We studied 201 unrelated French Basque individuals for HLA and Bf polymorphisms. The haplotypes of eighty-seven of them were deduced from family studies. The results show the frequency of the Bf F1 allele (0.1393) which is the highest one currently reported. They confirm the high frequencies of HLA-Aw19.2 and B18 previously reported in that population and show that a whole haplotype with strong linkage disequilibria, namely Aw19.2, Cw5, B18, Bf F1, DRw3 is frequent. On the other hand, the gene frequency of Bf S is decreased (0.5497) as compared with the other European Caucasoïd populations, while a slight increase in the Bf F gene frequency (0.2960) appears. These results point out that it is of importance to consider the genetic background choosing the population where linkage disequilibria are to be studied.

Alleles↗
PubMed1996

Detection of brain activation signal from functional magnetic resonance imaging data.

An image-processing strategy for functional magnetic resonance imaging (fMRI) data sets consisting of sequential images of the same slice of brain tissue is considered. An algorithm of detection based on the likelihood-ratio test and the noise properties in fMRI is introduced. Since the data have a poor signal-to-noise ratio, and in order to make detection reliable, the algorithm is organized in two steps: (1) pixel detection, which detects all pixels having significant changes, thus building regions of interest (ROIs), and (2) region detection, which selects the most likely activated region from obtained ROIs. The detection method is applied to experimental fMRI data from the motor cortex and compared with the cross-correlation method and Student's t test commonly applied by others. The results obtained using the likelihood-ratio test show improvement in the detection of activated regions.

Algorithms↗
PubMed2025

Characterization of FLOWERING LOCUS T-related genes and their putative gene regulatory network in semi-winter Brassica napus cultivar Zhongshaung11.

In many species, FLOWERING LOCUS T (FT)-like genes promote the floral transition by integrating environmental signals, in particular photoperiod, and internal cues. Here we show that Brassica napus contains six FT-like genes and two pseudogenes belonging to three orthogroups. All B. napus FT-like genes induce early flowering when expressed at the shoot apical meristems of Arabidopsis thaliana ft mutants; however, BnaFT.C6 and non-orthologous FT-like genes do not encode fully functional mobile florigens. In the case of BnFT.C6, the functional change is associated with a T to C amino acid change that is restricted to semi-winter accessions. Expression of orthologs of FT is photoperiod-dependent, and two distal enhancers are conserved; however, the homeologs BnaFT.A7 and BnaFT.C6 show rearrangements of DNA motifs binding NF-Y/CO and NF-Y transcriptional activator complexes between the promoter and downstream enhancers. Motif rearrangements correlate with differences in tissue-specific expression. Furthermore, homeologs with rearranged motifs could not be transactivated by B. napus CO in transient assays, although they show LD photoperiod-dependent expression. We propose that differential diurnal expression of NF-Y genes contributes to the photoperiod-dependent regulation of B. napus FT genes.

Brassica napus↗
PubMed2002

Interaural level differences and the level-meter model.

The interaural level difference (ILD) plays a significant role in sound localization. However, the definition of ILD for noise is open to some interpretation because it is not obvious how to deal with the inevitable level fluctuations. In this article, the ILD is interpreted as an energylike (time-integrated) measure of stimulus level, independent of other stimulus details-particularly interaural correlation. This concept is called the "level-meter model." The model was tested by measuring human ILD thresholds for noise stimuli that were interaurally correlated, or anticorrelated, or uncorrelated. An additional test (not involving lateralization) measured the threshold for level discrimination based on loudness. According to the level-meter model, all four thresholds should be the same. The experimental results showed that the predictions of the level-meter model held good to within about half a dB, although thresholds for level discrimination were systematically higher than ILDs. Among the ILDs themselves, thresholds were slightly higher for uncorrelated noise. The latter result could be explained by replacing the level-meter model with a loudness-meter model, incorporating temporal integration. The same model accounted for the bandwidth dependence of the threshold.

Adult↗
PubMed2003

On the detection of dispersion in the head-related transfer function.

Because of dispersion in head-related transfer functions (HRTFs), the interaural time difference (ITD) varies with frequency. This physical effect ought to have consequences for the size or shape of the auditory image of broadband noise because different frequency regions of the noise have different ITDs. However, virtual reality experiments suggest that human listeners are insensitive to head-related dispersion. The experiments of this article test that suggestion by experiments that isolate dispersion from amplitude effects in the HRTF and attempt to optimize the opportunity for detecting it. Nevertheless, the experiments find that the only effect of dispersion is to shift the lateralization of the auditory image. This negative result is explained in terms of the cross-correlation function for head-dispersed noise. Although the broad-band cross-correlation function differs considerably from 1.0, the cross-correlation functions within bands characteristic of auditory filters do not. A detailed study of the lateralization shifts show that the experimental shifts can be successfully calculated as an average of stimulus ITDs as weighted by Raatgever's frequency-weighting function (Thesis, Delft, The Netherlands, 1980).

Adult↗
PubMed1977

Group-specific component: evidence for two subtypes of the Gc1 gene.

A new method based on isofocusing electrophoresis in the study of the Gc (group-specific component) polymorphism, revealed differing electrophoretic patterns. These patterns can be explained by the existence of two codominant Gc1 subtypes. This hypothesis is in accordance with several family studies. These subtypes are called Gc1F and Gc1S. Eight hundred samples were analyzed, including three different populations: Caucasoid (a western Pyrenean valley), African (Pygmy Bi-Aka), and AMerindian (Quechua-Aymara, from Bolivia). These two subtype phenotypes cannot be explored with the usual technique. They were present in each population sample studied.

Africa↗