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Biomedical subjects

J M Meyer

Publications and source records attributed to J M Meyer.

At least 19 recordsLinked to original sources

Ferrisiderophore reductases of Pseudomonas. Purification, properties and cellular location of the Pseudomonas aeruginosa ferripyoverdine reductase.

Purification of the ferripyoverdine reductase from Pseudomonas aeruginosa, strain PAO1, lead to the isolation of a soluble protein of M(r) 27,000-28,000, as determined by HPLC sieving filtration and by denaturating gel electrophoresis. In the presence of NADH as the reductant, ferripyoverdine as the iron substrate, ferrozine as an iron(II)-trapping agent and FMN, this protein displayed an iron-reductase activity which resulted in the formation of ferrozine-iron(II) complex, providing that the enzymic assay was run under strict anaerobiosis. FMN was absolutely required for the activity to occur, but the lack of a visible spectrum and the lack of fluorescence for the protein in solution suggested that ferripyoverdine reductase is not a flavin-containing protein and that covalently bound FMN is not a prerequisite for the enzymatic reaction. A search of ferripyoverdine reductase by immunological detection amongst the different cellular compartments of P. aeruginosa lead to the conclusion that the soluble enzyme, which represented more than 95% of the total cellular enzyme, is not located in the periplasm but specifically in the cytoplasm. A strongly immunoreacting material, corresponding to a protein with identical M(r) as the ferripyoverdine reductase of P. aeruginosa PAO1, was detected in all the eighteen fluorescent pseudomonad strains belonging to the P. aeruginosa, P. fluorescens, P. putida and P. chlororaphis species, as well as in P. stutzeri, a non-fluorescent species, suggesting that the enzyme acting as a ferripyoverdine reductase in P. aeruginosa PAO1 is ubiquitous among the Pseudomonas.

Blotting, Western

Iron release from ferrisiderophores. A multi-step mechanism involving a NADH/FMN oxidoreductase and a chemical reduction by FMNH2.

Release of iron from various ferrisiderophores (ferripyoverdines, ferrioxamines B and E, ferricrocin, ferrichrome A, ferrienterobactin and its analog ferric N,N',N''-tri(1,3,5-Tris) 2,3-dihydroxybenzoylaminomethylbenzene) was obtained through an enzymic reduction of iron, involving NADH, FMN and the ferripyoverdine reductase of Pseudomonas aeruginosa PAO1. The iron released from the same complexes was also obtained through chemical reduction of iron involving FMNH2. Evidence is given that the enzymic process acts through a FMNH2 reduction; the P. aeruginosa enzyme, purified according to its ferripyoverdine-reductase activity [Hallé, F. & Meyer, J. M., Eur. J. Biochem. 209, 613-620], functions as a NADH:FMN oxidoreductase, the FMNH2 produced being able to chemically reduce the iron complexed by siderophores. The general occurrence of such a multi-step mechanism, which denies the existence of specific ferrisiderophore reductases, is discussed.

FMN Reductase

Using multidimensional scaling on data from pairs of relatives to explore the dimensionality of categorical multifactorial traits.

An accurate specification of the dimensionality and ordering of categorical multifactorial phenotypes (e.g., smoking status, including heavy, moderate, light, and nonsmokers) is an important prerequisite for the genetic analysis of these traits. Typically, phenotypic dimensionality and ordering are determined by comparing the relative fits of alternative parametric threshold models. Here, a method of analysis is described which addresses the same issue of trait dimensionality but does not require parametric assumptions. Specifically, we detail how nonmetric multi-dimensional scaling (MDS), applied to contingency tables which cross-classify the phenotypes or responses of one relative with another, may be used to explore trait dimensionality. Scaling results from deterministic simulation studies indicate that the latent structure of categorical phenotypes can be recovered with nonmetric MDS. Results from stochastic simulations, however, indicate that the accuracy of recovery, as well as the rejection of models of incorrect dimensionality, are strongly dependent upon sample size and the latent liability correlation between relatives. As an application of the method, the dimensionality of a measure of smoking status in 1,656 pairs of monozygotic twins ascertained through the American Association of Retired Persons is considered. The MDS results indicate that the onset of the smoking habit and the quantity smoked in this aging population represent a unidimensional process. The implication this finding has for subsequent genetic analysis is discussed.

Aged

Religion and education as mediators of attitudes: a multivariate analysis.

The transmission of social attitudes has been investigated as a possible model of cultural inheritance in a sample of 3810 twin pairs from the Australian National Health and Medical Research Twin Registry. Six social attitude factors were identified and univariate genetic models fitted to scores on each factor. A joint multivariate genetic analysis of the six attitude factors, church attendance, and education indicated that the attitudes were correlated--the same genes and shared environments influenced more than one attitude factor. A current controversy regarding social attitudes is whether the significant loadings on this shared environmental component represent true cultural influences or are actually the genetic consequences of phenotypic assortative mating for church attendance and educational attainment (Martin et al., 1986). In our data, church attendance is almost entirely due to the impact of the shared environment. The large shared environmental component on church attendance also accounts for a substantial part of the family resemblance in social attitudes, suggesting that not all of the apparent cultural effects found in earlier studies can be ascribed to the genetic effects of assortative mating. However, church attendance and education do not completely account for the cultural component. Therefore, effects in addition to church attendance, education, and assortative mating for church attendance and education must be involved in the cultural component of the inheritance of attitudes.

Adolescent

The relationship between age at first drug use and teenage drug use liability.

Our analyses of Carey's (1992) simulated data set of substance abuse in a cohort of adolescent twins were aimed at answering the question What is the relationship between age at first drug use and EVER having used drugs (i.e., teenage drug use liability)? Three analytic methods were used to determine whether age at first drug use was (1) a "perfect" index of drug use liability, (2) correlated in relatives but conditionally independent of drug use liability, or (3) causally influenced by drug use liability and by factors independent of liability. The analytic methods included nonmetric multidimensional scaling, multifactorial threshold model-fitting to contingency tables, and pedigree-based likelihood formulations for the raw data. All approaches indicated that age at first drug use was a perfect index of drug use liability. Further, model-fitting results indicated that only shared environmental factors accounted for twin similarity in the onset and timing of drug use. We discuss the limitations of each of the analytic methods and integrate our findings with the true model used in Carey's simulation.

Adolescent

Exogenous siderophore-mediated iron uptake in Pseudomonas aeruginosa: possible involvement of porin OprF in iron translocation.

In addition to the two siderophores pyoverdine and pyochelin synthesized by Pseudomonas aeruginosa ATCC 15692 (strain PAO1), several siderophores produced by other bacteria or fungi, namely cepabactin, salicylic acid, desferriferrichrysin, desferriferricrocin, desferriferrioxamine B, desferriferrioxamine E and coprogen, were able to promote iron uptake with variable efficiencies into this bacterium. For most of these siderophores, these results were consistent with the growth stimulation produced by the same compounds in a plate bioassay. Desferriferrichrome A, enterobactin and desferriferrirubin, however, did not promote iron uptake, although enterobactin and desferriferrirubin stimulated bacterial growth. These paradoxical data are discussed in view of siderophore-inducible iron uptake systems, as demonstrated recently for enterobactin. Among the strains tested, including the wild-type PAO1, the pyoverdine-less mutant PAO6606 and the two porin-mutants P. aeruginosa H636 (oprF::omega) and P. aeruginosa H673 (oprD::Tn501), only for the porin-OprF mutant were fewer siderophores able to promote iron uptake compared to the other strains. Such results suggest that beside specific routes for iron uptake P. aeruginosa is also able to take up siderophore-liganded iron through OprF.

Bacterial Outer Membrane Proteins

Cellular relationship impairment in maturation arrest of human spermatogenesis: an ultrastructural study.

Ultrastructural examination of testicular biopsies from cases of maturation arrest showed that there were characteristic abnormalities of the Sertoli cell junctional connections. These abnormalities together with the meiotic failure afford an explanation for the severe oligospermia or azoospermia noted in patients with maturation arrest. Premature setting up of ectoplasmic specializations in front of early spermatids and/or spermatocytes were also observed.

Adult

Iron metabolism in Pseudomonas: salicylic acid, a siderophore of Pseudomonas fluorescens CHAO.

Under iron-starvation conditions of growth, Pseudomonas fluorescens CHA0, a soil isolate involved in phytopathogenic fungi antagonisms, produced, together with pyoverdine, a second iron-chelating compound which was purified and identified by spectroscopy, HPLC and 1H-NMR to be salicylic acid. Mutants unable to synthesize pyoverdine overproduced this compound by a factor of 9-14. The biosynthesis of salicylic acid was under iron control; it was fully inhibited by 5 microM added iron in the growth medium. In contrast, salicylic acid of either bacterial or commercial origin facilitated labeled iron incorporation in iron-starved cells. Based on these two relationships observed with bacterial iron metabolism it is concluded that salicylic acid has a siderophore function for this strain.

Iron

Cholecystectomy by minilaparotomy without muscle section: a short-stay procedure.

The aim of this prospective study was to assess the results of cholecystectomy performed by an incision characterized by its small size and absence of muscle section, to minimize postoperative discomfort, and shorten hospital stay. Surgical access was via a transverse division of the linea alba extending 1.5-2 cm on the rectus sheath, on both sides, without section of muscle. One hundred and ninety-one patients were operated on. Only 1 (0.5%) peroperative complication (injury of cystic artery) and 4 (2%) benign postoperative complications occurred. The mean postoperative hospital stay was 4.4 +/- 1.7 days (range 2 to 12); for the 90 patients operated on in 1989-1990 it was 3.3 +/- 1.7 days (range 2 to 12). Long-term results were assessed in 113 patients. Only 1 (0.6%) complication occurred, namely migration of a retained common duct stone. Neither incisional hernias nor a need for reoperation occurred. The cosmetic results were assessed by the patients themselves as very good in 95 (84.1%) cases and good in 16 (14.2%) cases.

Adolescent

Estimating genetic influences on the age-at-menarche: a survival analysis approach.

A survival analysis regression model is described for analyzing twin data on the age-at-menarche. The model includes latent genetic and environmental covariates and allows one to test hypotheses regarding the nature of familial aggregation for age-at-onset. Additionally, the model accommodates a variety of baseline survival distributions and therefore may be used to test different developmental hypotheses. Model-fitting results indicate that a survival model with a baseline gamma distribution gives an adequate fit to recalled age-at-menarche of 1,888 pairs of Australian female monozygotic and dizygotic twins. Further, results show that additive genetic and dominance genetic effects contribute to shared variation in age-at-menarche. If there are common environmental influences on the timing of menarche, they are completely obscured by nonadditivity in genetic factors, and information from other relationships would be required to detect their effect.

Adolescent

A molecular genetic approach to the identification of isochromosomes of chromosome 21.

The largest class of de novo chromosomal rearrangements in Down syndrome are rea(21q21q). Classically, these rearrangements have been termed Robertsonian translocations, implying an attachment of two different chromosome 21 homologues. Additionally, a Robertsonian translocation between two chromosomes 21 cannot be distinguished from an isochromosome composed of genetically identical arms by cytogenetic analyses. Therefore, we have used molecular techniques to differentiate between true Robertsonian translocations and isochromosomes. Samples were obtained from 12 probands, ascertained for de novo rearrangements between homologous chromosomes 21 [11 rea(21q21q) and 1 rea (21;21)(q22;q22)], their parents (n = 24) and available siblings (n = 7). The parental origins of the de novo rearrangements were assigned using molecular and cytogenetic analyses. Although not statistically significant, there was a two-fold increase in the number of paternally derived de novo rearrangements (n = 8) as compared with maternally derived rearrangements (n = 4). To distinguish between rob(21q21q) and i(21q), we used restriction fragment length polymorphisms (RFLPs) spanning the length of chromosome 21. Using all informative and partially informative RFLPs, we used the method of maximum likelihood to assign the most likely rearrangement definition (i or rob) and parental origin in each family. The maximum likelihood estimates indicated that all rearrangements tested (n = 8) were isochromosomes. C-banding revealed two centromeres in three cases indicating that a U-type exchange occurred between sister chromatids in these rearrangements. Our results suggest that the majority of de novo rea(21q21q) are isochromosomes derived from a single parental chromosome 21.

Cells, Cultured

A model for comparative ratings in studies of within-family differences.

Comparative ratings between pairs of siblings or other relatives are commonly used to refine measures of intrafamily variation. A simple model, based on signal detection theory, is proposed which shows how comparative ratings can be used to estimate within-pair variances of true scores, which can, in turn, be modeled with any of the conventional approaches to partitioning genetic and environmental variance within families.

Humans

[Congenital insufficiency of the distal support function of the first ray of the foot].

Five patients with congenital deficiency of antero-medial support have been examined and treated at the Hôpital cantonal, Geneva. The main symptoms of these patients were global metatarsalgia and a dorsal bunion. All lesions were bilateral. Four of the patients had a localised dyslatia of the first ray, whereas one of them suffered from a nail patella syndrome. In two patients there was a hypoplastic first metatarsal, whereas in three others the first metatarsal was normal but too elevated under weight bearing. One patient responded well to conservative treatment. In three cases a lowering osteotomy of the first metatarsal bone with autologous bone graft was performed. The last patient was treated by arthrodesis between the first cuneiform and the first metatarsal for plantar-flexion the first ray. In one case it was necessary to transfer the long flexor of the great toe onto the first metatarsal according to Lapidus in combination with an arthrodesis of the great toe. One patient underwent an arthrodesis between the first cuneiform and the first metatarsal combined with an arthrodesis of the great toe. A Helal-type osteotomy on the second metatarsal was necessary in one case. The objective and subjective results were good or excellent. All treatments eliminated the painful symptoms, allowing all patients to resume a normal professional activity.

Foot Deformities, Congenital

Estimating familial effects on age at onset and liability to schizophrenia. II. Adjustment for censored data.

Genetic studies of disorders with adult onset often contain individuals who have not completed their age at risk when last observed. Without correction for such censoring, correlation in ages at onset among relatives is substantially underestimated. Moreover, without correction for the effect of correlated ages at onset, the relationship between age at onset in the proband and liability in relatives is substantially overestimated. The present paper describes methods for correcting the effects of censoring on these estimates. In a companion paper [Kendler and MacLean, Genet Epidemiol 7:409-417, 1990] these methods are applied to a large family study of schizophrenia.

Adolescent

Measurement of immunoreactive angiotensin II levels in microdissected brain nuclei from developing spontaneously hypertensive and Wistar Kyoto rats.

Levels of immunoreactive angiotensin II (ANG II) were measured in specific microdissected nuclei from the brains of newborn (NB; less than 1 week of age), 4-, 8-, and 12-week-old spontaneously hypertensive rats (SHR) and their age-matched normotensive controls, Wistar Kyoto (WKY) rats, using a sensitive radioimmunoassay. The structures investigated included the paraventricular nucleus of the hypothalamus (PVH), the nucleus of the solitary tract (NTS), the dorsal motor nucleus of the vagus (DMN of X), the locus coeruleus (LC), and the A1 region of the medulla. A section of cerebellar cortex was used as a control. Although ANG II was detected in each of the nuclei examined, there were no differences in the ANG II contents of any of these structures between young (NB and 4 week old) SH and WKY rats. However, by 8 weeks of age, the SHR had significantly higher ANG II levels in the PVH, NTS, and DMN of X than its normotensive control, and at 12 weeks of age, significantly higher ANG II levels were observed in the PVH, NTS, DMN of X, and LC of the SHR compared to those in the WKY. During the developmental period under investigation, both strains revealed increases in the ANG II content of all nuclei except for the LC, where the ANG II levels decreased with age. No detectable ANG II was found in the cerebellar cortex of either strain at any age.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II

Polymerization shrinkage of index and pattern acrylic resins.

Inadequate dimensional stability caused by polymerization shrinkage has been reported concerning the various applications of acrylic resins. The objective of the study was to evaluate dimensional changes of two self-curing acrylic resins marketed as pattern and index material. Early volumetric changes were measured with a dilatometer and late linear changes were recorded with an inductive transducer. After 24 hours the volumetric shrinkage was 7.9% for Duralay resin and 6.5% for Palavit G resin; 80% of the change appears before 17 minutes at room temperature. Shrinkage was significantly increased when the proportion of powder in the mix was diminished. Results suggest that these resins should be used with some method to compensate for the shrinkage, when used as index material. However, the dimensional change might provide significant advantages for intracoronal castings.

Acrylic Resins

Genetic and environmental effects on self-reported depressive symptoms in a general population twin sample.

To determine the etiology of self-reported depressive symptoms and their co-occurrence in the general population, multivariate genetic models were fitted to the responses of 771 female twin pairs (463 MZ, 308 DZ) to a 20-item epidemiological depression inventory (CES-D scale). A model which contained one common genetic factor, one shared environmental factor, and four unique environmental factors provided a useful account of symptom covariation. Under this model, the four non-shared environmental factors explained the largest proportion of variance in response to the CES-D scale, whereas a single common genetic factor explained substantially less of the variation in symptomatology. Consistent with previous findings (Kendler, Heath, Martin, & Eaves, Archives of General Psychiatry 43, 213-221, 1986) shared environmental influences were found to play a relatively minor role in the report of depressive symptoms. These results suggest that while genetic factors do contribute to the covariation among symptoms of depression, it is the largely non-shared environmental factors that account for the co-occurrence of symptoms in the general population.

Adolescent