Biomedical subjects

J M Meyer

Publications and source records attributed to J M Meyer.

At least 19 recordsLinked to original sources

PubMed2001

Fine-scale mapping of a locus for severe bipolar mood disorder on chromosome 18p11.3 in the Costa Rican population.

We have searched for genes predisposing to bipolar disorder (BP) by studying individuals with the most extreme form of the affected phenotype, BP-I, ascertained from the genetically isolated population of the Central Valley of Costa Rica (CVCR). The results of a previous linkage analysis on two extended CVCR BP-I pedigrees, CR001 and CR004, and of linkage disequilibrium (LD) analyses of a CVCR population sample of BP-I patients implicated a candidate region on 18p11.3. We further investigated this region by creating a physical map and developing 4 new microsatellite and 26 single-nucleotide polymorphism markers for typing in the pedigree and population samples. We report the results of fine-scale association analyses in the population sample, as well as evaluation of haplotypes in pedigree CR001. Our results suggest a candidate region containing six genes but also highlight the complexities of LD mapping of common disorders.

Alleles↗

PubMed2001

Tumor necrosis factor markers show sex-influenced association with rheumatoid arthritis.

OBJECTIVE: The observation that not all shared-epitope genotypes confer the same risk suggests that a second HLA-region locus may confer risk. Tumor necrosis factor alpha (TNFgamma) is a possible candidate. We examined TNFalpha for sex influences on HLA-associated risk for rheumatoid arthritis (RA). METHODS: DRB1 and TNF microsatellite typing of 297 Caucasian RA patients (132 men, 165 women) and 267 Caucasian controls was performed. RESULTS: The TNFab microsatellite haplotype distribution differed among the male RA, female RA, and control groups (P < 0.01); the difference was largely an excess of TNFa2b1 haplotypes in the male RA group. However, this did not simply reflect an excess of shared-epitope haplotypes bearing TNFa2b1. In RA, not all shared-epitope-bearing haplotypes had the same TNFab. The *0401-bearing haplotypes commonly had TNFa6b5, TNFa2b1, TNFa10b4, and TNFa11b4, while the *0404-bearing haplotypes had TNFa11b4. In the female RA group, TNFa2b1 was most often on *0401-bearing haplotypes. In the male RA group, there was a surprise: TNFa2b1 was often on HLA haplotypes without shared-epitope DRB1 alleles. To estimate the relative strength of associated HLA markers, we performed logistic regression analyses stratified by sex and controlling for a potential confounder, age at disease onset. Among women, TNFa2b3 favored RA (odds ratio 1.932, P < 0.05) while TNFa6b5 was protective (odds ratio 0.522, P < 0.05). Among males, TNFa2b1 and TNFa11b4 conferred elevated odds ratios (2.58 and 1.681, respectively, P < 0.05). However, the odds ratios for TNFa2b1 in men and TNFa2b3 in women were generally well below those for RA-associated DRB1 markers (for example, DRB1*0401 3.553 in male RA patients and 6.991 in female RA patients). CONCLUSION: Certain TNFab-bearing HLA haplotypes modify RA risk in a manner influenced by sex but independent of DRB1, particularly TNFa2b1 in men.

Alleles↗

PubMed2001

Missense polymorphism in the human carboxypeptidase E gene alters enzymatic activity.

Carboxypeptidase E (CPE) is involved in the biosynthesis of peptide hormones and neurotransmitters, including insulin. One of the features of type 2 diabetes mellitus (T2DM) is an elevation in the proinsulin level and/or proinsulin/insulin molar ratio, suggesting that mutations in proinsulin processing enzymes may contribute to the development of T2DM. We scanned CPE for mutations in a collection of Ashkenazi T2DM families and identified five novel single nucleotide polymorphisms (SNPs). An SNP in the 283(rd) codon, c.847C>T, changes arginine to tryptophan (R283W). The residue Arg283 is conserved among CPE orthologs as well as most enzymatically active metallocarboxypeptidases. Of the 272 Ashkenazi T2DM pedigrees screened, we found four families segregating R283W. Within these four families, patients who inherited one copy of this variant had much earlier age of onset for T2DM. The R283W CPE protein cleaves peptide substrates with substantially lower efficiencies and is less stable at elevated temperature. In addition, the R283W CPE variant has a narrower pH optimum and is much less active at pH 6.0-6.5, indicating that the R283W CPE variant would be substantially less active than wild type CPE in the trans-Golgi network and immature secretory vesicles where the enzyme functions in vivo. To summarize, we uncovered a rare non-conservative missense mutation in CPE and demonstrated that the mutant protein has altered enzymatic properties. We predict that this mutant could cause hyperproinsulinism and diabetes in the homozygous state.

5' Untranslated Regions↗

PubMed2001

Study of pyoverdine type and production by Pseudomonas aeruginosa isolated from cystic fibrosis patients: prevalence of type II pyoverdine isolates and accumulation of pyoverdine-negative mutations.

The lungs of cystic fibrosis patients are frequently colonized by Pseudomonas aeruginosa, which produces high-affinity fluorescent peptidic siderophores, pyoverdines. Three pyoverdines which differ in their peptide chain and are easily differentiated by isoelectric focusing exist, only one being produced by a given strain. P. aeruginosa isolates from cystic fibrosis patients of a German hospital were analyzed by sequential, pulse-field gel electrophoresis (PFGE) and for pyoverdine production and type. Only producers of type I and type II pyoverdine were found. There was a perfect correlation between the type of pyoverdine produced and the clonality determined by PFGE. PFGE clone C, the most prevalent among cystic fibrosis patients, and found in an aquatic environment, produced type II pyoverdine. Pyoverdine-negative mutants seemed to increase as a function of the lung colonization time, but retained the capacity to take up pyoverdines. Most isolates that took up type II pyoverdine were also able to utilize type I pyoverdine as judged by growth stimulation experiments. No correlation was observed between the loss of pyoverdine production and mucoidy.

Cystic Fibrosis↗

PubMed2001

Corrosion behavior of a welded stainless-steel orthopedic implant.

The corrosion behavior of combinations of materials used in an orthopedic implant: the spherical part (forged or forged and annealed) constituting the head, the weld (tungsten inert gas (TIG) or electron beam (EB) techniques), and the cylindrical part (annealed) constituting the shaft of a femoral prosthesis - has been investigated. Open-circuit potentials, potentiodynamic curves, Tafel slope, mixed potential theory and susceptibility to intergranular attack are electrochemical and chemical procedures selected for this work. Electrochemical measurements using a microelectrode have been made in the following zones: spherical part, cylindrical part, weld, and weld/sphere, and weld/shaft interfaces. To detect intergranular attack, the Strauss test has been used. At the interfaces, corrosion currents, measured (Icorr) and predicted (Icouple) are low, in the order of the pico- to nanoampere. The electrochemical behavior of the electron beam (EB) weld is better than that of the tungsten inert gas (TIG). Welds at interfaces can behave either anodically or cathodically. It is better if welds, which are sensitive parts of the femoral prosthesis, behave cathodically. In this way, the risk of starting localized corrosion (pitting, crevice or intergranular corrosion) from a galvanic couple, remains low. From this point of view, the sample with the EB weld offers the best behavior. All the other samples containing a TIG type of weld exhibit a less favorable behavior. The mechanical treatments (forged, and forged and annealed) of the steel sphere did not show any difference in the corrosion behavior. No intergranular corrosion has been observed at the weld/steel interface for unsensitized samples. With sensitized samples, however, a TIG sample has exhibited some localized intergranular corrosion at a distance of 500 microm along the weld/stainless steel (sphere) interface.

Biocompatible Materials↗

PubMed2001

Bond strength of composite to dentin using conventional, one-step, and self-etching adhesive systems.

OBJECTIVES: This in vitro study compared the dentin bonding performance of eight adhesive systems using a microtensile bond strength test. METHODS: Thirty bovine teeth were ground to 600-grit to obtain flat root-dentin surfaces. Two conventional adhesive systems (Scotchbond Multipurpose Plus, OptiBond FL), four one-step adhesive systems (Scotchbond 1, Asba S.A.C., Prime and Bond NT, Excite) and two self-etching adhesive materials (Clearfil Liner Bond 2 V and Prompt L-Pop) were evaluated. Each bonding system was applied according to manufacturer's instructions and followed by composite (Z100) application. Immediately after bonding, the teeth were prepared for microtensile testing. Bond strength to dentin was measured using a Vitrodyne V-1000 universal tester. There were 14 replicates for each material. Fractured specimens were further observed by SEM. RESULTS: Scotchbond Multipurpose Plus exhibited significantly (p<0.05) higher bond strength values (30.3+/-9.4 MPa) than all other materials. The bond strengths of the other materials were (from highest to lowest): Opitbond FL (22.4+/-4.3 MPa); Scotchbond 1(18.9+/-3.2); Clearfil Liner Bond 2 V (18.9+/-3.0); Prime and Bond NT (18.3+/-6.9); Asba S.A.C. (14.4+/-2.9); Excite (13.8+/-3.7); and Prompt L-Pop (9.1+/-3.3). Statistical comparisons frequently overlapped, but Optibond was significantly (p<0.05) greater than Asba, Excite, and Prompt L-Pop; whereas, Scotchbond 1 was only significantly (p<0.05) greater than Prompt L-Pop. Asba, Excite and Prompt L-Pop were not significantly different. The fracture modes were mostly adhesive. CONCLUSIONS: The conventional adhesive systems produced higher bond strengths to root dentin than most one-step adhesives and one self-etching adhesive; with the exception of one material in each respective system.

Adhesiveness↗

PubMed2001

Genetic and environmental influences on the relationship among combat exposure, posttraumatic stress disorder symptoms, and alcohol use.

The role of genetic and environmental influences on the relationship between combat exposure, posttraumatic stress disorder (PTSD) symptoms, and alcohol use were examined in 4072 male-male twin pairs who served in the United States military during the Vietnam era (1965-1975). Results indicate that the relationship between combat and alcohol use and between PTSD symptom factors and alcohol use were both substantially influenced by genetic factors. Findings are most consistent with a shared vulnerability model for the etiology of the association between PTSD symptoms and alcohol use. Specific unique environmental factors were more important than genetic factors for PTSD symptoms, and both factors were equally important for alcohol use. Further support is also found for the role of the unique environment in PTSD symptoms.

Alcoholism↗

PubMed2001

The structure of a pyoverdine produced by a Pseudomonas tolaasii-like isolate.

Cultures of Agaricus bisporus, the most extensively cultivated mushroom, can be infected severely by Pseudomonas tolaasii. This pathogen is characterized by the so-called white line reaction, a precipitate formed on agar plates between its colonies and those of P. reactans, both belonging to the collective species P. fluorescens. A recent study has shown that a group of P. tolaasii isolates can be subdivided into two groups or 'siderovars', based on the pyoverdines they produce (Munsch et al. 2000). One group of strains is characterized by the pyoverdine described by Demange et al. (1990). A representative of the second group (strain Ps3a) was found to produce the same pyoverdine as a strain which had been classified before as P. aureofaciens. However, based mainly on 16S rRNA gene sequence comparisons and REP-PCR generated fingerprints, the two strains are not identical. They are also distinguishable from the P. tolaasii type strain.

Agaricales↗

PubMed2001

Helicobacter pylori and early duodenal ulcer status post-treatment: a review.

BACKGROUND: Data submitted to the FDA were reviewed to analyze the relationship between Helicobacter pylori infection and the incidence of early duodenal ulcers, within 6 weeks, following treatment. MATERIALS AND METHODS: Retrospective analyzes were performed on data from three H. pylori development programs submitted to the FDA: ranitidine-bismuth-citrate (RBC), lansoprazole (L) and omeprazole (O). Efficacy assessments for the RBC, L and O programs were made at end of a 4-week treatment period, 4-6 weeks following the end of a 14-day treatment period, and 4 weeks following the end of a 4-week treatment period, respectively. RESULTS: Overall, there was a 15%, 21% and 23% decrease in the number of patients in the RBC, L and O programs, respectively, with ulcers among H. pylori cleared/eradicated patients post-treatment compared with patients with persistent infection. Among patients who did not have cleared/eradicated H. pylori in the RBC and O programs, where antisecretory agents were continued beyond the antimicrobial treatment period, the number of ulcers was lower in the antisecretory plus antimicrobial subgroups compared with the antimicrobial alone subgroups (37% vs. 46% for RBC and 33% vs. 42% for O). Among patients with cleared/eradicated H. pylori, the number of patients with ulcers in the antimicrobial alone subgroups and antisecretory plus antimicrobial subgroups were similar within each program. Antimicrobials alone had significantly lower rates of ulcers among patients with cleared/eradicated H. pylori as compared with patients without clearance/eradication. CONCLUSIONS: The early incidence of duodenal ulcers is significantly decreased in patients with H. pylori clearance/eradication.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2001

Navi-ball: a new guidance device for CT-directed punctures.

RATIONALE AND OBJECTIVES: A new navigation system (Navi-Ball) for computed tomography (CT)-guided punctures was tested clinically. METHODS: The device consists of a transparent hemisphere with an angular scale. The hemisphere is fluid filled and contains a bubble indicating the angulation. The system works as a circular spirit level. Adapted to the handle of the needle, it allows needle adjustment according to the planned puncture path on the CT image. The system was tested in 36 patients who had 40 procedures. The needle deviation (in relation to the planned course of the needle) was measured in two rectangular planes. RESULTS: Without requiring preparation time, the guidance system allowed rapid and easy performance of the puncture. First-time needle placement in a double-angulated approach led to a deviation of the needle from the planned path ranging from 0.2 degrees to 4.6 degrees (mean 2.1 degrees, SD 1.4 degrees ) in the axial plane and from 0.4 degrees to 4.0 degrees (mean 2.3 degrees, SD 1.2 degrees). CONCLUSIONS: This "low-tech" system offers easy to use guidance by a single operator and provides for adequate accuracy of first-time needle placement.

Equipment Design↗

PubMed2001

Improved in-stent magnetic resonance angiography with high flip angle excitation.

RATIONALE AND OBJECTIVES: To optimize the intraluminal signal intensity of a nitinol stent by performing contrast-enhanced three-dimensional magnetic resonance angiography (CE-MRA) with varying flip angles (FAs). METHODS: Contrast-enhanced magnetic resonance angiography at 1.5 T and FAs of 30 degrees, 100 degrees, and 150 degrees was performed on five sheep with 10 iliac nitinol stents (Memotherm-FLEXX). Maximum-intensity projections (MIPs) and composite images of MIPs were performed and compared. RESULTS: Reconstructed MIPs at an FA of 150 degrees showed a slightly disturbed lumen visibility inside the stent accompanied by low-grade lumen visibility outside the stent and vice versa for an FA of 30 degrees. Composite images of a 30 degrees MIP added to a 150 degrees MIP resulted in improved image quality compared with the standard MIP of a single FA. CONCLUSIONS: Signal loss due to radiofrequency shielding inside nitinol stents imaged by CE-MRA can be reduced by applying high FAs. Composite MIP images allow simultaneous visualization of the lumen inside as well as outside the stent.

Alloys↗

PubMed2001

Novel antipsychotics and severe hyperlipidemia.

Newer atypical antipsychotics demonstrate superior effectiveness, with a diminished incidence of extrapyramidal side effects compared with older typical antipsychotics, but they have been associated with the development of obesity and new-onset diabetes. A small number of reports documenting modest hypertriglyceridemia related to newer antipsychotics have implicated fluperlapine, clozapine, and, most recently, olanzapine. This study summarizes the results of 14 cases of severe hypertriglyceridemia (>600 mg/dL) associated with olanzapine and quetiapine therapy occurring among inpatients at Oregon State Hospital, including 7 patients whose serum triglyceride levels exceeded 1,000 mg/ dL. Four of these patients also developed new-onset diabetes. Nine cases occurred during the first 8 months of treatment, with three cases identified within 3 months of commencing olanzapine or quetiapine therapy. Weight gain in olanzapine and quetiapine groups was modest (12.3 lb and 8.5 lb, respectively) and did not correlate with the severity of hypertriglyceridemia. Biochemical causes for severe hypertriglyceridemia associated with novel antipsychotics are unclear, but clinical monitoring of serum lipids must be added to the concerns about the metabolic consequences of therapy with certain newer antipsychotic agents.

Adolescent↗

PubMed2001

Cell-matrix interactions and cell-cell junctions during epithelial histo-morphogenesis in the developing mouse incisor.

The continuously growing rodent incisor develops mainly along its antero-posterior axis. The labio-lingual asymmetry which characterizes this tooth is initiated at the cap stage and increases further during the cap to bell transition (ED14 to ED16) when histogenesis of the enamel organ proceeds. Histology, transmission electron microscopy (TEM), and immunostaining were used to document the changes in the basement membrane (BM) as well as the modifications of epithelial cell-matrix and cell-cell interactions during this period. The expression of plakoglobin, desmoglein and E-cadherin at ED14 suggested that the main cell-cell junctional complexes were adherens junctions. The expression of desmoglein and TEM observations suggested a progressive antero-posterior stabilization of the enamel organ by means of desmosomes from ED14 to ED18. alpha6 integrin, BP 230 and laminin gamma2 chain were all expressed in the developing incisor but were not always co-distributed. Immunostaining and TEM suggested that only primitive type II hemidesmosomes were present. At ED14, cells of the enamel knot (EK) did not show any specific expression for antigens involved in cell-cell interaction. However, strong staining for the laminin gamma2 chain characterized the BM in contact with EK cells. The BM in the labial part of the cervical loop demonstrated ultrastructural changes: the presence of loops of the lamina densa in this region preceeded the differential expression of the integrin alpha6 subunit and that of the laminin gamma2 chain in the labial/lingual parts of the cervical loop. Apoptosis was transiently observed in the contiguous mesenchyme. This affected osteoblasts and also nerve cells close to the labial part of the cervical loop.

Animals↗

PubMed2000

Twin study of adolescent genetic susceptibility to mosquito bites using ordinal and comparative rating data.

Ordinal and comparative rating measures of mosquito attraction and mosquito bite frequency and symptoms were administered in a self-report questionnaire format to a sample of 197 monozygotic and 326 dizygotic Australian adolescent twin pairs at age 12 between 1992 and 1999, in order to investigate the environmental and possibly genetic determinants of variation between individuals. Repeat measures were obtained from the twin pairs at age 14. Ordinal variable measures, although providing some support for genetic effects on mosquito susceptibility, were affected by low repeatability. However, analysis of a comparative rating variable "compared with your twin, who is bitten by mosquitoes more often?" indicated a strong genetic influence on frequency of being bitten by mosquitoes, with no significant differences observed between males and females. Comparative rating questionnaire items are a potentially valuable tool for complementing and improving the results obtained from more conventional absolute measures.

Adolescent↗

PubMed2000

Pyoverdines: pigments, siderophores and potential taxonomic markers of fluorescent Pseudomonas species.

Pyoverdine, the yellow-green, water-soluble, fluorescent pigment of the fluorescent Pseudomonas species, is a powerful iron(III) scavenger and an efficient iron(III) transporter. As a fluorescent pigment, it represents a ready marker for bacterial differentiation and, as a siderophore, it plays an important physiological function in satisfying the absolute iron requirement of these strictly aerobic bacteria. Close to 40 structurally different pyoverdines have been identified to date, each characterized by a different peptidic part of the molecule and by a very narrow specificity as an iron transporter for Pseudomonas species, usually restricted to the producer strain or to strains producing an identical compound. Cross-reactivity does occur, however, for pyoverdines exhibiting partial identity at the peptide chain level, suggesting some information on the receptor-recognition site of the molecule. With the recent description of an operonic cluster of four genes involved in the synthesis of the chromophoric part of the molecule, a total of seven pyoverdine biosynthetic genes have been identified so far in Pseudomonas aeruginosa PAO1. Although the precise function of the gene products needs further clarification, a biosynthetic pathway based on a multienzyme thiotemplate mechanism allowing a step-by-step synthesis of the whole chromopeptide molecule can be postulated. A promising future is expected from recent developments which indicate that pyoverdines might be considered as potent and easy-to-handle taxonomic markers for the fluorescent species of the genus Pseudomonas.

Bacterial Typing Techniques↗

PubMed2000

High-resolution electron-microscopic study of the relationship between human enamel and dentin crystals at the dentinoenamel junction.

The development of dentin and of enamel share a common starting locus: the dentinoenamel junction (DEJ). In this study the relationship between enamel and dentin crystals has been investigated in order to highlight the guiding or modulating role of the previously mineralized dentin layer during enamel formation. Observations were made with a high-resolution electron microscope and, after digitalization, image-analysis software was used to obtain digital diffractograms of individual crystals. In general no direct epitaxial growth of enamel crystals onto dentin crystals could be demonstrated. The absence of direct contact between the two kinds of crystals and the presence of amorphous areas within enamel particles at the junction with dentin crystals were always noted. Only in a few cases was the relationship between enamel and dentin crystals observed, which suggested a preorganization of the enamel matrix influenced by the dentin surface structure. This could be explained either by the existence of a proteinaceous continuum between enamel and dentin or by the orientation of enamel proteins by dentin crystals.

Crystallization↗

PubMed2000

Effect of sub-lethal concentrations of HEMA (2-hydroxyethyl methacrylate) on THP-1 human monocyte-macrophages, in vitro.

OBJECTIVE: Resin monomers such as HEMA (2-hydroxyethyl methacrylate) can be released from restorative materials and diffuse into the tooth pulp over long periods of time. Although the short-term toxicity of resin monomers has been well documented, little is known about the risk for chronic toxicity resulting from low concentrations of resins. Thus, the hypothesis tested in this study was that sub-lethal concentrations of HEMA alter the functions of macrophages after long-term exposure. METHODS: Human THP-1 monocyte-macrophages were exposed to concentrations of HEMA between 0 and 1.5 mmol/l for up to 6 weeks. Cellular proliferation was measured by a hemocytometer with trypan-blue dye exclusion. Mitochondrial activity was measured by the MTT assay, and total cellular protein was measured using the bicinchoninic acid assay. RESULTS: Macrophage proliferation was inhibited 40-50% (significant, p < 0.05) by as little as 0.75 mmol/l after 1 week of exposure. Inhibition of proliferation remained constant after 1 week. The total protein per cell increased by as much as 80% (significant, p < 0.05) after 2 weeks and remained elevated through 6 weeks. Mitochondrial activity per cell increased 60-80% (significant, p < 0.05) after 2 weeks, then decreased. However, mitochondrial activity remained significantly elevated above controls through 6 weeks. SIGNIFICANCE: Findings from the current study indicate that 6-week exposures of monocytes to HEMA alter their proliferation and other activities at concentrations substantially lower than previously reported. This is particularly relevant in light of evidence that such concentrations have been previously shown to come through dentin by diffusion.

Analysis of Variance↗

PubMed2000

Familial aggregation for conduct disorder symptomatology: the role of genes, marital discord and family adaptability.

BACKGROUND: There is extensive evidence of statistical associations between family discord/ maladaptation and antisocial behaviour in the children, but questions remain on the extent to which the psychopathological risks are genetically or environmentally mediated. METHODS: Twin pairs (N = 1,350), aged 8 to 16 years, in the general population-based Virginia Twin Study of Adolescent Behavioral Development were assessed using the Child and Adolescent Psychiatric Assessment interview administered separately to both twins and both parents. Structured interviews for parental lifetime psychiatric disorders were also administered to the mothers and fathers. Maternal reports on Olsson's Family Adaptability and Cohesiveness questionnaire and the Dyadic Adjustment Scale were used as indices of the family environment. A path analytical model based on an extended twin-family design was used to test hypotheses about parent offspring similarity for conduct disorder symptomatology. RESULTS: Family discord and maladaptation, which intercorrelated at 0.63, were associated with a roughly two-fold increase in risk for conduct disorder symptomatology. When parental conduct disorder was included in the model the environmental mediation effect for family maladaptation remained, but that for family discord was lost. CONCLUSION: It is concluded that there is true environmental mediation from family maladaptation, operating as a shared effect, which accounts for 3.5 % of the phenotypic variance. The assumptions underlying this genetic research strategy are made explicit, together with its strengths and limitations.

Adaptation, Psychological↗