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PubMed2004

Line-bisecting performance in highly skilled athletes: Does preponderance of rightward error reflect unique cortical organization and functioning?

A line-bisecting test was administered to 250 highly skilled right-handed athletes and a control group of 60 right-handed age matched non-athletes. Results revealed that athletes made overwhelmingly more rightward errors than non-athletes, who predominantly bisected lines to the left of the veridical center. These findings were interpreted in the context of previous EEG research on athletes and brain localization studies of select personality traits. A preliminary theory (Group Cortical Organization and Activation Theory) that highly skilled athletes and other specific homogeneous populations may have developed a unique cortical organization or response system that mediates relative tendencies in cerebral activation was advanced. The potential utility of the line-bisecting test as an assessment and intervention tool in sports was discussed.

Cerebral Cortex↗
PubMed2006

Polar flagellum biogenesis in Aeromonas hydrophila.

Mesophilic Aeromonas spp. constitutively express a single polar flagellum that helps the bacteria move to more favorable environments and is an important virulence and colonization factor. Certain strains can also produce multiple lateral flagella in semisolid media or over surfaces. We have previously reported 16 genes (flgN to flgL) that constitute region 1 of the Aeromonas hydrophila AH-3 polar flagellum biogenesis gene clusters. We identified 39 new polar flagellum genes distributed in four noncontiguous chromosome regions (regions 2 to 5). Region 2 contained six genes (flaA to maf-1), including a modification accessory factor gene (maf-1) that has not been previously reported and is thought to be involved in glycosylation of polar flagellum filament. Region 3 contained 29 genes (fliE to orf29), most of which are involved in flagellum basal body formation and chemotaxis. Region 4 contained a single gene involved in the motor stator formation (motX), and region 5 contained the three master regulatory genes for the A. hydrophila polar flagella (flrA to flrC). Mutations in the flaH, maf-1, fliM, flhA, fliA, and flrC genes, as well as the double mutant flaA flaB, all caused loss of polar flagella and reduction in adherence and biofilm formation. A defined mutation in the pomB stator gene did not affect polar flagellum motility, in contrast to the motX mutant, which was unable to swim even though it expressed a polar flagellum. Mutations in all of these genes did not affect lateral flagellum synthesis or swarming motility, showing that both A. hydrophila flagellum systems are entirely distinct.

Aeromonas hydrophila↗
PubMed2001

Construction of adenoviral vectors.

Recombinant adenovirus vectors have proven to be useful tools in facilitating gene transfer. Construction of such vectors requires a knowledge of the adenovirus genome structure and its life cycle. A commonly used recombinant adenovirus involves deletion of the E1 region; such a recombinant is traditionally produced by overlap recombination after cotransfection of 293 cells with a plasmid shuttle vector and a large right-end restriction fragment of viral DNA. The shuttle vector contains a cassette for a transgene placed in region E1 and flanking sequences from adenovirus for recombination. Normally, a high background of parental virus results because of the difficulty in separating right-end restriction fragment length DNA from uncut DNA. This paper describes a negative selection based on the traditional cotransfection method using viral DNA from an E1-deleted adenoviral recombinant that expresses green fluorescent protein (GFP). In situ fluorescent microscopy is used to distinguish the recombinant plaques (white or nonfluorescent) from the parental virus plaques (green or fluorescent). In addition, this system allows for the detection of contaminating parental virus at later stages when production lots of the recombinant vector are being made.

Adenoviridae↗
PubMed2001

Kallmann syndrome: towards molecular pathogenesis.

Gonadotropin Releasing Hormone (GnRH) is a key regulator of reproduction and sexual behaviour. During the last decade, embryological studies have clarified the question of the early development of GnRH-synthesising neurones before the onset of neurosecretion. These studies have revealed the existence of a topographical link between GnRH-synthesising neurones and the embryonic olfactory system, thereby shedding new light on Kallmann syndrome, a developmental disease characterised by the association of hypogonadotropic hypogonadism and anosmia (or hyposmia). Although Kallmann syndrome was identified as an inherited disease in the forties, familial cases of the disease are infrequent. However, the identification, by positional cloning strategies, of the gene underlying the X-chromosome linked form of the disease (KAL-1) has opened the way to molecular pathophysiology. KAL-1 encodes an extracellular glycoprotein of compound modular structure. The protein, named anosmin-1, has been produced in a transfected mammalian cell line and purified. Polyclonal and monoclonal antibodies have been generated, which allowed us to study the distribution of the protein during the period of human organogenesis (4--10 embryonic weeks), by immunohistofluorescence. During this developmental period, anosmin-1 is a locally restricted component of various extracellular matrices (interstitial matrices and basement membranes). Later in embryonic life, KAL-1 expression apparently becomes restricted to definite neuronal populations. Based on the distribution of anosmin-1 in the early olfactory system, the pathogenesis of the olfactory loss and GnRH deficiency in X-linked Kallmann syndrome is discussed.

Cell Adhesion Molecules↗
PubMed1991

Impedance measurements in the human right ventricle using a new pacing system.

A promising new pacemaker that provides on-line measurements of right ventricular (RV) impedance was evaluated in ten patients with symptomatic second- or third-degree atrioventricular (AV) block. We tested the assumption that if changes in RV impedance represented changes in RV stroke volume (SV), conditions known significantly to affect RV SV should be accompanied by significant changes in RV impedance. One week after pacemaker implantation, RV impedance was measured noninvasively during normal respiration in the supine (baseline), left lateral, right lateral, sitting, and standing positions. In addition, all patients performed a Valsalva maneuver test. The amplitude of the impedance signal was different during in- and expiration in every body position studied. At baseline, the amplitude of the signal was 18.80 +/- 2.24 mm; in the right lateral position 16.75 +/- 3.24 mm (P = 0.04) and 17.80 +/- 2.35 mm in the left lateral position (P = 0.04). The amplitude of the signal in the sitting position was 16.65 +/- 2.89 mm (P = 0.07) and in the standing position 16.95 +/- 3.44 mm (P = 0.11). The most impressive change in amplitude was noted during performance of the Valsalva maneuver. During this test the amplitude decreased to 13 +/- 2.81 mm and rose to 20 +/- 2.66 mm (P = 0.002) afterwards. These results strongly support the assumption that changes of RV impedance as measured by this catheter represent changes in RV SV. This new pacing system is the first pacemaker that reports on the hemodynamic response of every heartbeat by measuring RV impedance.

Aged↗
PubMed1995

Distribution of cranial and rostral spinal nerves in tadpoles of the frog Discoglossus pictus (Discoglossidae).

We studied the peripheral nervous system of early tadpoles of the frog Discoglossus pictus using whole-mount immunohistochemistry. Double-labeling of muscles and nerves allowed us to determine the innervation of all cranial muscles supplied by the trigeminal, facial, glossopharyngeal, vagal, and hypoglossal nerves. The gross anatomical pattern of visceral, cutaneous, and lateral-line innervation was also assessed. Most muscles of the visceral arches are exclusively supplied by posttrematic rami of the corresponding branchiomeric nerves, the only exceptions being some ventral muscles (intermandibular, interhyoid, and subarcual rectus muscles). In the mandibular arch, the pattern of motor ramules of the trigeminal nerve prefigures in a condensed form the adult pattern, but the muscles of the hyoid arch are innervated by ramules of the facial nerve in a pattern that differs from that of postmetamorphic frogs. With respect to the nerves of the branchial arches, pretrematic visceral rami, typical of other gnathostomes, are absent in D. pictus. Instead, we find a separate series of posttrematic profundal visceral rami. Pharyngeal rami of all branchial nerves contribute to Jacobson's anastomosis. We provide a detailed description of the lateral-line innervation and describe a new ramus of the middle lateral-line nerve (ramus suprabranchialis). We confirm the presence of a first spinal nerve and its contribution to the hypoglossal nerve in D. pictus tadpoles.

Animals↗
PubMed1994

Etl2, a novel putative type-I cytokine receptor expressed during mouse embryogenesis at high levels in skin and cells with skeletogenic potential.

The regulatory effects of signaling proteins like hormones, growth factors, and cytokines are mediated by specific cell surface receptors which are grouped into distinct families on the basis of structural criteria. Here we report on the isolation and embryonic expression of a novel mouse gene, Etl2 (enhancer trap locus 2) which, based on its deduced amino acid sequence, constitutes a new member of the cytokine type-I receptor family. Among type-I receptors Etl2 is most similar to the alpha subunits of the human ciliary neurotrophic factor (CNTF) receptor and the mouse interleukin-6 (IL6) receptor with 32 and 30% identical amino acids, respectively. From Day 9 p.c. (postcoitum) onward low levels of Etl2 mRNA were detected in mesenchymal cells throughout the embryo and in parts of the nervous system, in particular in the ependymal linings of the spinal cord and the developing brain vesicles and in the neuronal layer of the retina. Highest levels of Etl2 expression were found on Day 12.5 p.c. in the craniofacial mesenchyme and during subsequent development in mesenchymal cells around all developing cartilages. At later stages, Etl2 transcripts were abundant in the dental papilla, the dermis, and hair follicles, as well as in the perichondrium and periost, i.e., in regions containing chondro and osteo progenitor cells. Etl2 mRNA was not detected, however, in mature odontoblasts, chondroblasts, osteoblasts, chondrocytes, and osteocytes. Our results suggest that Etl2 is a new orphan receptor belonging to the type-I cytokine receptor family and that Etl2 might have regulatory functions, particularly in the control of proliferation and/or differentiation of skeletogenic progenitor and other mesenchymal cells.

Amino Acid Sequence↗
PubMed1999

[Occupationally-induced contact dermatitis and bronchial asthma in a unusual delayed reaction to hydroxychloroquine].

We report the case of a a 60 year-old worker in the pharmaceutical industry who suffered from recurring contact dermatitis. Initially the contact dermatitis was limited to the hands; later on it became generalized. The patient had been working on a drug filling line in a pharmaceutical plant for more than 20 years. Eight years after starting this job he had developed allergic hand dermatitis to 2,6-diaminopyridine (patch test positive); this healed upon cessation of exposure. Ten years later he again developed hand dermatitis which progressed to generalized dermatitis and conjunctivitis. Under systemic and local therapy with corticosteroids and cessation of work, it healed nearly completely. Four months after returning to work, the patient experienced a first episode of severe asthma and generalized dermatitis with conjunctivitis following exposure to hydroxychloroquine the day before. The asthma and dermatitis improved after systemic corticosteroid therapy and stopping work. His condition continued to fluctuate, when though the patient was transferred at work and now wore rubber gloves. Eight months later he again developed a generalized dermatitis. Patch testing revealed delayed-type sensitizations to hydroxychloroquine (tested in concentrations of 0. 1%, 0.5%, 1% and 2%). Equivalent tests in five healthy volunteers were negative. The patch test reactions were pustular, while a biopsy was interpreted as a multiform contact dermatitis reaction. Bronchial exposure with hydroxychloroquine dust produced a delayed bronchial obstruction over the next 20 hours, which progressed to fever and generalized erythema (hematogenous contact dermatitis). After removing exposure to 2,6-diaminopyridine and hydroxychloroquine, the patient went on to develop a contact dermatitis to latex (patch test positive). However, skin prick tests with latex and patch tests with rubber additiva were negative. Hydroxychloroquine is well known to cause drug reactions. To our knowledge, contact dermatitis to this substance has not yet been reported. It is noteworthy that the patch test reactions were pustular and of multiform morphology and that bronchial exposure to the allergen resulted in asthma and a generalized drug reaction. Pathogenetically the asthmatic reaction seems to be on a delayed-type mechanism as is also seen with ampicillin, cobalt and nickel induced asthma.

Asthma↗
PubMed1996

Intermediate results of the extracardiac Fontan procedure.

BACKGROUND: Fourteen children (ages 2 to 14 years) and 1 adult (32 years) have undergone a modification of the Fontan procedure in which an extracardiac lateral tunnel or conduit is used in combination with staged or simultaneous bidirectional Glenn shunt(s). METHODS: Extracardiac lateral tunnels (n = 9) were constructed using a polytetrafluoroethylene patch (n = 7), pericardial patch (n = 1), or in situ pericardial flap (n = 1). Extracardiac lateral conduits (n = 6) were constructed using nonvalved homografts (n = 2) or polytetrafluoroethylene tube grafts (n = 4). Fenestrations were created in 4 patients (2 each in extracardiac lateral tunnel and extracardiac lateral conduit patients). Aortic cross-clamping was completely avoided in 12/15 patients (aortic cross-clamping in 2 patients for atrial septal defect enlargement and 1 for Damus-Kaye-Stansel procedure). RESULTS: There have been no operative deaths. Prolonged postoperative chest tube drainage (> 2 weeks) has been rare (n = 1). At follow-up (range, 6 to 54 months; mean, 27.5 months), all patients are in New York Heart Association class I or II and remain in normal sinus rhythm. Late protein-losing enteropathy was seen in 1 patient and was successfully treated by percutaneous creation of a stented fenestration from the extracardiac tunnel to the systemic atrium. Late catheterizations reveal unobstructed extracardiac lateral tunnel function and low pulmonary pressures (range, 11 to 13 mm Hg). Advantages of the extracardiac Fontan include (1) avoidance of aortic cross-clamping in most patients, (2) the hemodynamic benefits of total cavopulmonary connection, (3) avoidance of atriotomy and intraatrial suture lines, (4) preservation of sinus rhythm and no arrhythmias at 2 year follow-up, (5) drainage of the coronary sinus to low pressure atrium, (6) allowance for early/late fenestrations, (7) prevention of baffle leaks and intraatrial obstruction, and (8) allowance for growth (tunnel procedures only). CONCLUSIONS: We recommend this extracardiac procedure for all suitable patients undergoing surgical conversion to the Fontan circulation.

Adolescent↗
PubMed2004

Recall bias of the symptoms of nausea and vomiting of pregnancy.

OBJECTIVE: Nausea and vomiting of pregnancy is the most common medical condition in pregnancy. Relatively little research has been conducted on this condition, and much of it is based on women's reports. Determinants that affect women's reports of their nausea and vomiting of pregnancy symptoms have not been elucidated. The purpose of this study was to assess the accuracy of recall by women of their symptoms of nausea and vomiting of pregnancy. STUDY DESIGN: Two hundred women who called the Motherisk nausea and vomiting of pregnancy counseling line in Toronto were asked about the severity of their nausea and vomiting of pregnancy symptoms with the use of the pregnancy unique quantification of emesis and nausea system (PUQE). The patients were asked the same questions again during a follow-up call, which took place up to 16 weeks later. RESULTS: There was a recall (or reporting) bias for nausea and vomiting, with women reporting significantly more severe symptoms during their follow-up call than they had reported originally. Multivariate analysis revealed that the severity of the symptoms affected the accuracy of recall positively, whereas the time that has elapsed affected it negatively. CONCLUSION: Retrospective evaluation of nausea and vomiting of pregnancy symptoms may produce a recall bias, which may distort the evaluation of the therapeutic effectiveness of antiemetics.

Female↗
PubMed1999

Is Schizophrenia a lateralized brain disorder? Editor's introduction.

Lateralization of brain function was established on the basis of clinical-pathological correlations over a century ago. In the past two decades, this line of research has attempted to link the complex behaviors evident in schizophrenia to the failure to develop and maintain a normal pattern of hemispheric activity. This issue of Schizophrenia Bulletin reviews and presents data from multiple perspectives of methods applied to the study of laterality in schizophrenia. Brain disorders affecting systems that modulate complex behavior are commonly related to laterality. Therefore, this dimension of brain function merits further investigation in schizophrenia.

Cerebral Cortex↗
PubMed2005

Molecular characterization, phylogenetic relationships, and developmental expression patterns of prion genes in zebrafish (Danio rerio).

Prion diseases are characterized by the accumulation of a pathogenic misfolded form of a prion protein (PrP) encoded by the Prnp gene in humans. In the present study in zebrafish, two transcripts and the corresponding genes encoding prion proteins, PrP1 and PrP2, related to human PrP have been characterized with a relatively divergent deduced amino acid sequence, but a well preserved overall organization of structural prion protein motifs. Whole-mount in situ hybridization analysis performed during embryonic and larval development showed a high level of PrP1 mRNA spatially restricted to the anterior floor-plate of the central nervous system and in ganglia. Transcripts of prp2 were detected in embryonic cells from the mid-blastula transition to the end of the segmentation period. From 24 h postfertilization up to larval stages, prp2 transcripts were localized in distinct anatomical structures, including a major expression in the brain, eye, kidney, lateral line neuromasts, liver, heart, pectoral fins and posterior intestine. The observed differential developmental expression patterns of the two long PrP forms, prp1 and prp2, and the short PrP form prp3, a more divergent prion-related gene previously identified in zebrafish, should contribute to understanding of the phylogenetic and functional relationships of duplicated prion gene forms in the fish genome. Together, the complex history of prion-related genes, reflected in the deduced structural features, conserved amino acid sequence and repeat motifs of the corresponding proteins, and the presence of differential developmental expression patterns suggest possible acquisition or loss of prion protein functions during vertebrate evolution.

Amino Acid Sequence↗
PubMed2001

Progression of lymphomatoid papulosis to systemic lymphoma is associated with escape from growth inhibition by transforming growth factor-beta and CD30 ligand.

Our objective is to understand the mechanism of progression of lymphomatoid papulosis (LyP) to CD30+ systemic lymphoma. LyP lesions appear in recurrent crops that regress, only to reappear at a later date in the same or different locations. About 10% of patients develop systemic lymphoma. Because transforming growth factor-beta (TGF-beta) and CD30 ligand inhibit the growth of normal lymphocytes and can be detected in regressing lesions of LyP, we tested the effect of these cytokines on cell lines clonally derived from LyP in the progression to systemic lymphoma. TGF-beta failed to inhibit the growth of lymphoma cells from advanced disease due to mutations of the TGF-beta receptor complex that prevented binding of the ligand to tumor cells. A CD30 ligand agonist antibody caused proliferation of tumor cells from one patient and had no effect on tumor cells of another. In contrast, a Fas agonist antibody caused significant growth inhibition of all cell lines. The results suggest that progression of LyP to lymphoma is associated with escape of lymphoma cells from growth regulation by TGF-beta and CD30 ligand.

Antibodies↗
PubMed2002

Liver X receptors in the central nervous system: from lipid homeostasis to neuronal degeneration.

Liver X receptors (LXRalpha and -beta) are nuclear receptors abundant in the liver where they are regulators of lipid homeostasis. Both LXRs are also expressed in the brain, but their roles in this tissue remain to be clarified. We examined the brains of mice in which the genes of both LXRalpha and -beta have been disrupted and found several severe abnormalities. One of the most striking features is that the lateral ventricles are closed and lined with lipid-laden cells. In addition, there are enlarged brain blood vessels, especially in the pars reticularis of the substantia nigra and in the globus pallidus. Other features of the brains are excessive lipid deposits, proliferation of astrocytes, loss of neurons, and disorganized myelin sheaths. Electron micrographs revealed that, as mice aged, lipid vacuoles accumulated in astrocytes surrounding blood vessels. Comparison of mRNA profiles in LXR knockout mice and wild-type littermates showed that expression of several LXR target genes involved in cholesterol efflux from astrocytes was reduced. These findings show that LXRs have an important function in lipid homeostasis in the brain, and that loss of these receptors results in neurodegenerative diseases. Further characterization of the role of LXRs in the brain could lead to new insights into the etiology and treatment of some neurodegenerative disorders.

Animals↗
PubMed2002

Functional MRI of language: new approaches to understanding the cortical organization of semantic processing.

Until recently, our understanding of how language is organized in the brain depended on analysis of behavioral deficits in patients with fortuitously placed lesions. The availability of functional magnetic resonance imaging (fMRI) for in vivo analysis of the normal brain has revolutionized the study of language. This review discusses three lines of fMRI research into how the semantic system is organized in the adult brain. These are (a) the role of the left inferior frontal lobe in semantic processing and dissociations from other frontal lobe language functions, (b) the organization of categories of objects and concepts in the temporal lobe, and (c) the role of the right hemisphere in comprehending contextual and figurative meaning. Together, these lines of research broaden our understanding of how the brain stores, retrieves, and makes sense of semantic information, and they challenge some commonly held notions of functional modularity in the language system.

Brain Mapping↗
PubMed2003

Head development in the onychophoran Euperipatoides kanangrensis with particular reference to the central nervous system.

The neuroectoderm of the Euperipatoides kanangrensis embryo becomes distinguishable during germ band formation when the antennal segment is evident externally. During later stages of development, the neuroectoderm proliferates extensively and, at the anterior part of the head, newly-formed neuron precursor cells occupy most of the volume. The antenna forms from the dorsolateral side of the anterior somite. The antenna has no neuroectoderm of its own at the onset of its formation, but instead, neurons migrate out to the appendage from the nearby region of the developing brain. When the antennal tract is formed it is positioned horizontally in the brain, in line with the antennal commissure. Only later, and coincidentally with the anterior repositioning of the antenna, is the tract's distal part bent anteriorly and positioned laterally. The eye starts to develop posteriorly to the antenna and the antennal commissure. This suggests that the segment(s) associated with the onychophoran eye and antenna are not serially homologous with segments carrying equivalent structures within the Euarthropoda. Evidence is presented to further support the presence of a terminal mouth in the ground plan of the Onychophora and, hence, an acron may not exist in the arthropod clade.

Animals↗
PubMed1989

Development of consultation-liaison psychiatry in The Netherlands. Its social psychiatric heritage.

Dutch consultation-liaison psychiatry (C-L psychiatry) has followed a developmental line separate from the American system. First, C-L psychiatry in the Netherlands has been less influenced by psychosomatic medicine than by social psychiatry. Second, the presence of psychiatric units in general hospitals that appear to be correlated with the growth of C-L psychiatry in the United States occurred later in the Netherlands. Third, little government support for clinical care, research, and especially for training has been available to Dutch psychiatry. Consequently, there has been little recent financial pressure on C-L psychiatry from reduced government support, as occurred in the United States. Finally, the relationship between primary and secondary health care in the Netherlands allows C-L psychiatry to have a direct impact on several inpatient and ambulatory levels in the health care chain. A nationally accepted database form for the computerized registration of the Psychiatric Consultations at the eight university hospitals and ten other general hospitals is currently in use. To facilitate standardization and recording the psychiatric consultation process, the Netherlands Consortium for C-L psychiatry (NCCP) was formed.

Humans↗
PubMed1994

Developmental dyslexia, neural timing and hemispheric lateralisation.

Approximately 5% of 8-10-year-olds experience exceptional difficulties learning to read (developmental dyslexia). This usually has a congenital basis; it runs in families, and affects 4 times as many boys as girls. Dyslexics typically show impairment both in phonemic segmentation (the subdivision of speech beyond the natural syllabic level) and in sequencing small visual symbols. Both these skills draw upon the ability of the nervous system to time sensory events precisely. A specific magnocellular cell type which expresses a distinctive surface antigen plays a crucial role in these functions. The development of this cell line is probably congenitally impaired in dyslexics. Visually they have lowered flicker and motion sensitivity, and disorder of the magnocellular layers of the Lateral Geniculate Nucleus can be seen post mortem. Likewise they have lowered sensitivity to changes in frequency and amplitude of sounds, hence impaired discrimination of speech sounds. These disorders are associated with abnormal hemispheric lateralisation in these subjects, e.g. dyslexics show reduction or reversal of the usual left > right asymmetry of the planum temporale. Many of these characteristics of impaired magnocellular function and reversed hemispheric asymmetry are found not only in dyslexic children but also in developmental dysphasics, autistics, high schizotypes and schizophrenics. I will speculate therefore that normal magnocellular development promotes normal hemispheric asymmetry and that impaired magnocellular development is responsible for a spectrum of problems associated with impaired hemispheric specialisation, ranging from the mildest, dyslexia, to the most severe, schizophrenia.

Adolescent↗