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Biomedical subjects

T Becker

Publications and source records attributed to T Becker.

At least 19 recordsLinked to original sources

Axonal regrowth after spinal cord transection in adult zebrafish.

Using axonal tracers, we characterized the neurons projecting from the brain to the spinal cord as well as the terminal fields of ascending spinal projections in the brain of adult zebrafish with unlesioned or transected spinal cords. Twenty distinct brain nuclei were found to project to the spinal cord. These nuclei were similar to those found in the closely related goldfish, except that additionally the parvocellular preoptic nucleus, the medial octavolateralis nucleus, and the nucleus tangentialis, but not the facial lobe, projected to the spinal cord in zebrafish. Terminal fields of axons, visualized by anterograde tracing, were seen in the telencephalon, the diencephalon, the torus semicircularis, the optic tectum, the eminentia granularis, and throughout the ventral brainstem in unlesioned animals. Following spinal cord transection at a level approximately 3.5 mm caudal to the brainstem/spinal cord transition zone, neurons in most brain nuclei grew axons beyond the transection site into the distal spinal cord to the level of retrograde tracer application within 6 weeks. However, the individually identifiable Mauthner cells were never seen to do so up to 15 weeks after spinal cord transection. Nearly all neurons survived axotomy, and the vast majority of axons that had grown beyond the transection site belonged to previously axotomized neurons as shown by double tracing. Terminal fields were not re-established in the torus semicircularis and the eminentia granularis following spinal cord transection.

Afferent Pathways

Is computerized tomography ventricular abnormality related to cycloid psychosis?

Twenty-eight psychiatric patients with computerized tomography (CT) findings of ventricular abnormality most likely to result from prenatal/perinatal lesions (VA group) were compared to 28 sex- and age-matched psychiatric patients with normal neuroradiological findings (NCT group). The neuroradiological rater was blind to clinical psychiatric diagnoses and, vice versa, clinical diagnoses were established without knowledge of neuroradiological findings. A polydiagnostic approach (DSM-III-R, ICD-10, Leonhard Classification) was used for psychiatric diagnostic workup. Significantly more patients with cycloid psychoses (according to Leonhard's original description) were found in VA as compared to NCT patients. According to DSM-III-R and ICD-10, VA and NCT groups did not differ significantly regarding diagnostic distribution. Ventricular abnormalities that may reflect sequels of birth complications and/or adverse events during pregnancy may constitute one of the risk factors for developing cycloid psychosis as originally described by Leonhard.

Adult

Insertional mutagenesis in zebrafish identifies two novel genes, pescadillo and dead eye, essential for embryonic development.

Recently our laboratory described an efficient method for generating retroviral provirus insertions in the zebrafish germ line, and we showed that provirus insertions induce embryonic mutations at a frequency of roughly one mutant per 70 insertions. To date we have isolated four insertional mutants and, using the proviruses as a molecular tag, have cloned the genes disrupted in three of them. The proviruses in all three mutants lie within or just 5' of the first coding exon, point in the opposite transcriptional orientation from the gene, and disrupt transcription. Here we present a molecular characterization of two genes identified by this method and describe the associated mutant phenotypes. The pescadillo (pes) gene is predicted to encode a protein of 582 amino acids with no recognizable functional motifs, which is highly conserved from yeast to humans. pes mRNA is expressed widely and dynamically during the first 3 days of embryogenesis. Prominent sites of expression are the eyes and optic tectum on day 1, the fin buds, liver primordium, and gut on day 2, and the branchial arches on day 3. Beginning at day 3 of embryogenesis, pes mutant embryos exhibit small eyes, a reduced brain and visceral skeleton, shortened fins, and a lack of expansion of the liver and gut, and then die on the sixth day of development. The dead eye (dye) gene encodes a protein of 820 amino acids that is homologous to genes of unknown function in human, mouse, and Xenopus, and that has weak homology with the yeast NIC96 (nucleoporin-interacting component) gene. dye mutants can be recognized on day 2 of embryogenesis by the presence of necrotic cells in the tectum and eyes. dye mutants die on day 5 of development. These results demonstrate the power of insertional mutagenesis in zebrafish for rapidly finding and characterizing novel genes essential for embryonic development. Using our current methodology, we estimate that our laboratory could screen approximately 25,000 insertions in 2-3 years, identifying perhaps 250-350 embryonic lethal genes. Assuming that all genes are accessible to proviral insertion, the wider application of this approach could lead to the rapid identification of the majority of genes that are required for embryonic development of this vertebrate.

Amino Acid Sequence

Insertional mutagenesis and rapid cloning of essential genes in zebrafish.

Large-scale chemical mutagenesis screens in zebrafish have led to the isolation of thousands of lethal mutations in genes that are essential for embryonic development. However, the cloning of these mutated genes is difficult at present as it requires positional cloning methods. In Drosophila, chemical mutagenesis screens were complemented with P-element insertional mutagenesis which facilitated the cloning of many genes that had been identified by chemical lesions. To facilitate the cloning of vertebrate genes that are important during embryogenesis, we have developed an insertional mutagenesis strategy in zebrafish using a retroviral vector. Here, in a pilot screen of 217 proviral insertions, we obtained three insertional mutants with embryonic lethal phenotypes, and identified two of the disrupted genes. One of these, no arches, is essential for normal pharyngeal arch development, and is homologous to the recently characterized Drosophila zinc-finger gene, clipper, which encodes a novel type of ribonuclease. As it is easy to generate tens to hundreds of thousands of proviral transgenes in zebrafish, it should now be possible to use this screening method to mutate and then rapidly clone a large number of genes affecting vertebrate developmental and cellular processes.

Amino Acid Sequence

Confirmation of reduced temporal limbic structure volume on magnetic resonance imaging in male patients with schizophrenia.

A structural deficit in the temporal lobes has been implicated in the pathogenesis of schizophrenia. A prospective magnetic resonance imaging (MRI) study was carried out in 20 young male patients with schizophrenia and 20 age-matched healthy male volunteers. Volumetric measurements were performed in all slices with temporal lobe cross-sections from the temporal pole to the tip of the Sylvian fissure. Volumetric assessment included the temporal lobe as a whole, hippocampal formation and amygdala complex, temporal horn and cella media of the lateral ventricle, the third ventricle, and hemispheric volume in all slices that showed temporolimbic structures. Brain structural deficit in the patients was most conspicuous in the posterior portion of the hippocampal formation. Significant effects of diagnosis were also found for the total temporal lobe and the third ventricle. Multiple regression analysis revealed posterior hippocampal volume to be significantly determined by diagnosis, but not by age or by temporal lobe or hemispheric volume. Significant correlations of morphologic and clinical parameters were restricted to negative correlations of temporal lobe volume with the global rating and sum score of the Scale for the Assessment of Negative Symptoms. The study confirms subtle temporolimbic deficit reported in previous MRI studies in patients with schizophrenia.

Adult

The polysialic acid modification of the neural cell adhesion molecule is involved in spatial learning and hippocampal long-term potentiation.

The alpha-2,8-linked polysialic acid (PSA) modification of the neural cell adhesion molecule (NCAM) modulates morphogenetic cell interactions. PSA is strongly expressed during neural development and generally down-regulated in the adult. However, it remains prominent in some areas of the brain, e.g., the hippocampus. We assayed the functional role(s) of PSA in synaptic plasticity in the hippocampus in two experimental paradigms by removing PSA with endo-neuraminidase NE (endo-N) an enzyme which specifically cleaves alpha-2,8-linked polysialic acid. (1) The acquisition and retention of spatial memory of rats in the Morris water maze, critically dependent on the hippocampus, was significantly impaired after a localized injection of endo-N into the hippocampus, whereas visual and motor capacities were unaffected. (2) Tetanic stimulation of the Schaffer collaterals in endo-N-treated hippocampal slices in vitro failed to elicit LTP and yielded only a short post-tetanic potentiation, but the response returned to control levels within 2 minutes, whereas basal synaptic activity and short-term potentiation were not affected. Our findings suggest that the carbohydrate epitope PSA plays an important role in synaptic plasticity.

Analysis of Variance

[Ulcer healing through the elimination of Helicobacter pylori: is a week of therapy enough?].

AIM OF STUDY: To test whether one week's triple therapy with omeprazole and two antibiotics is enough to induce healing of a peptic (gastric and/or duodenal) ulcer. PATIENTS AND METHODS: 112 Patients (73 males, 39 females; median age 55 [18-88] years) proven by culture or histology to have an Helicobacter (H.) pylori infection and uncomplicated peptic (gastroduodenal) ulcer. For one week they received omeprazole (20 mg once or twice daily) plus two antibiotics (clarithromycin/metronidazole, clarithromycin/tetracycline, clarithromycin/amoxycillin or amoxycillin/metronidazole) to eradicate H. pylori. No further anti-ulcer treatment was given subsequently. Healing of the ulcer and H. pylori status were checked by the urease test, culture and histology (endoscopic biopsy) 4 weeks later. RESULTS: The 5-week ulcer healing rate was 94.6% (95% confidence interval: 89-98%). Persisting ulcers (n = 6) were associated with either treatment with aspirin or nonsteroidal antiinflammatory drugs (n = 3), persistent H. pylori infection (n = 2) or persistent H. pylori infection plus treatment with aspirin (n = 1). The ulcer healing rate was significantly higher in patients with eradicated infection than in those with posttherapy persistence of H. pylori (97.0 vs. 76.9%; P = 0.02). There were no significant differences after 5 weeks between patients with duodenal and those with gastric ulcer (97.4 vs. 89.3%). CONCLUSIONS: One-week effective eradication treatment is adequate to induce healing of H. pylori-positive peptic ulcers. Anti-ulcer treatment after eradication of H. pylori should be considered only if the patient is receiving treatment with ulcerogenic drugs or continues to have symptoms.

Adolescent

Differential ontogenic pattern of metabotropic [3H]-L-glutamate receptors in normal and granule cell-deficient mouse cerebellum.

[3H]-L-glutamate binding site distribution corresponding to metabotropic receptors was studied by autoradiography during normal and altered cerebellar ontogeny in mice treated on postnatal days (PND) 5 and 6 with the antimitotic methylazoxymethanol (MAM). Quisqualate (QA)-induced and (2S,3S,4S)-alpha-(carboxycyclopropyl)-glycine (L-CCG-I)-induced [3H]-L-glutamate binding inhibition allowed us to distinguish between group I and group II metabotropic receptor binding sites. In control cerebellar cortex, the QA-sensitive binding site density increases during development, while the L-CCG-I-sensitive binding site density decreases. In the deep cerebellar nuclei (DCN), both populations of binding sites decrease during ontogeny. The antimitotic treatment induces: (1) a slight but significant increase in the QA-sensitive binding sites in the DCN at PND 10 and in the cerebellar cortex beginning from PND 20; (2) a retarded decrease in the L-CCG-I-sensitive metabotropic receptor binding site density. These differences could be due to a retarded cell maturation and/or an over-expression of some postsynaptic receptors in the adult cerebellum in response to the afference deficiency.

Amino Acids, Dicarboxylic

One-week triple therapy with omeprazole, amoxycillin and either clarithromycin or metronidazole for cure of Helicobacter pylori infection.

AIM: The present study was designed to evaluate the efficacy and tolerability of 1-week triple therapy regimens for Helicobacter pylori. METHODS: In two consecutive series, 120 patients with proven H. pylori infection and peptic ulcer disease or functional dyspepsia were treated with either omeprazole 20 mg b.d., amoxycillin 1 g b.d. and clarithromycin 250 mg b.d. (OAC; n = 60) or with omeprazole 20 mg b.d., amoxycillin 1 g b.d. and metronidazole 400 mg b.d. over 1 week (OAM; n = 60). H. pylori infection was assessed by rapid urease test, culture and histology before and 4 weeks after cessation of the eradication therapy. RESULTS: H. pylori eradication succeeded in 53 out of 60 patients by omeprazole-amoxycillin-clarithromycin (OAC) (88%; 95% CI 77-95%) and in 47 out of 60 patients by omeprazole-amoxycillin-metronidazole (OAM) (78%; 95% CI 66-88%) (P = 0.22). Nine patients of each group available for follow-up reported adverse events (15.0 and 15.5%, respectively) without necessity of discontinuation of the study medications. Serious adverse events were not observed. CONCLUSIONS: Simple and convenient 1-week triple therapies consisting of omeprazole, amoxycillin and either clarithromycin or metronidazole are sufficiently effective in eradicating H. pylori infection.

Adolescent

[Acute organic psychosis after malaria tropica].

Neuropsychiatric complications in the course of plasmodium falciparum infection are usually summarized as cerebral malaria. Heterogeneous clinical symptoms, different courses and inconstant parasitemia, however, suggest different pathogenic mechanisms. We report a case of an acute symptomatic psychosis occurring two weeks after successful therapy of a primary manifestation of plasmodium falciparum infection. The diagnosis of meningoencephalitis was based on lymphocytic pleocytosis of cerebrospinal fluid and hyperintense lesions in cranial magnetic resonance imaging. Due to the lack of plasmodium falciparum parasitemia and of serological evidence of viral infection a final diagnosis was not possible. Considering the pertinent literature, an immune-mediated complication of plasmodium falciparum infection (acute disseminated encephalomyelitis, ADEM) appears to be more probable than a direct viral or plasmodium CNS infection. We propose to reverse the term cerebral malaria for the cases with direct pathogenic influence of plasmodium falciparum, and to distinguish it from cases with possible immune-mediated pathogenesis.

Adult

[Psychiatric sequelae of craniocerebral trauma--a review of the literature].

In a brief review psychiatric aspects of head-injured patients are discussed. The topic is put into a historical perspective. Examples of recent developments in head-trauma research are given. Differentiation between focal and diffuse brain injury is suggested to be of clinical relevance. Little is known as yet about the neuropsychologic and psychiatric sequelae of diffuse axonal injury to the brain.

Brain Concussion

Cerebellar arachnoid cyst in a firesetter: the weight of organic lesions in arson.

A 52-year-old female patient was accused of arson; the patient had had an arachnoid cyst of the cerebellar vermis. Even after surgery, she showed marked instability of mood and pseudologia fantastica, but did not suffer from cognitive impairment. Possible associations of the presence of this cerebellar arachnoid cyst and behavioral disturbances are discussed.

Arachnoid Cysts

Association of anophthalmia and esophageal atresia.

We report on a boy and a girl with bilateral anophthalmia and proximal esophageal atresia. In addition to vestigial optic nerves and chiasma, MRI studies showed other central nervous system abnormalities; one had ectopic tissue in the hypothalamic region, and the other hand generalized ventriculomegaly associated with atrophy. Two other cases, both males, have been reported with anophthalmia and esophageal atresia as their only malformations. These 4 cases are reviewed in light of recent advances in the understanding of ocular embryogenesis and of the midbrain as a development field. Concurrence of these defects appears to be non-random.

Anophthalmos

Immunohistological localization of tenascin-C in the developing and regenerating retinotectal system of two amphibian species.

The expression pattern of the extracellular matrix molecule tenascin-C was investigated in the retinotectal system of the frog Discoglossus pictus and the salamander Pleurodeles waltl during development and optic nerve regeneration in the adult. In both species, the retina was devoid of tenascin-C immunoreactivity at all ages studied. During development, tenascin-C was distributed in a gradient in the optic nerve, with the highest immunoreactivity in the eye near part of the optic nerve. The myelin-associated glycoprotein was distributed in a gradient with opposite polarity. In Discoglossus, but not Pleurodeles, tenascin-C was detected in the anterior chiasm. In the tectum of both species, tenascin-C was observed in deep cellular and fiber layers but not in the layers receiving optic fibers or proliferative zones. The distribution patterns of tenascin-C were the same during development and in the adult, except for a disappearance of the molecule from the intraocular part of the optic nerve. After lesioning the optic nerve of adult animals, tenascin-C was strongly reexpressed in the intraocular part of the optic nerve but was only weakly upregulated in the distal optic nerve stump. In contrast, a chondroitin sulfate epitope was strongly upregulated in the distal optic nerve stump. These observations suggest that during development, tenascin-C serves as an attenuating barrier for myelinating cells in the optic nerve and contributes to the guidance of growing retinal ganglion cell axons. Due to its sustained expression in the adult, tenascin-C may have similar functions during regeneration of the lesioned adult retinotectal system.

Animals

Reduced echogenicity of brainstem raphe specific to unipolar depression: a transcranial color-coded real-time sonography study.

Echogenicity of the brainstem raphe was assessed in patients with major depression, bipolar affective disorders, and schizophrenia and compared with healthy adults employing transcranial color-coded real-time sonography. Forty probands were enrolled in each group. A highly significant reduction in raphe echogenicity was detected only in patients suffering from major depression. Echogenicity of the raphe was independent of age or sex and did not correlate with severity of the depressive syndrome or patient state. These findings are suggestive of structural desintegration of the brainstem raphe in unipolar depression, an anatomical region assumed to be a biological focus in the pathogenesis of depressive syndromes.

Adult

D- and L-lactate determination in dairy products: presentation of a fast automated analysis system.

A flow-injection system is presented, which is versatile, automated and has an integrated enzyme system. Its efficiency at determining D- and L-lactate separately in dairy products is compared with the officially used reference method (DIN 10335). By means of a mathematical elimination of matrix effects, the pretreatment steps can be clearly reduced. As a result of the immobilization of the enzymes, an appropriate automation software and an adaptation of the system developed to the given medium, the analysis could be performed within 5 min and was distinctly cheaper than alternative methods. The values determined in 15 different dairy products deviated from those of the reference method by 3% at a maximum.

Animals

Some methodological issues in neuroradiological research in psychiatry.

An outline is given of some of the methodological issues discussed in neuroradiological research on psychiatric illness. Strengths and shortcomings of magnetic resonance imaging (MRI) in depicting and quantifying brain structures are described. Temporal lobe anatomy and pathology are easily accessible to MRI, whereas limits on anatomical delineation hamper approaches to frontal lobe study. White matter hyperintense lesions are sensitively depicted by MRI, but specificity is limited. Distinction of vascular and primary degenerative dementia is considerably improved by CT and MRI analysis. Computed tomography (CT) and MRI have enhanced the understanding of treatable organic psychiatric disorders, e.g., normal pressure hydrocephalus. Subcortical and white matter pathology has been replicated in CT and MRI studies of late-onset psychiatric disorders, clinical overlap with cerebrovascular disease or neurodegeneration may be of import. Transcranial sonography findings of brainstem structural change specific to unipolar depression may contribute to the understanding of affective psychoses. Magnetic resonance spectroscopy and functional MRI are likely to stimulate psychiatric research in the future.

Brain

Disturbances of cerebrospinal fluid (CSF) circulation--neuropsychiatric symptoms and neuroradiological contribution.

The present study aimed at relating dementia, pseudo-neurasthenic and affective organic brain syndromes to underlying type of CSF flow disorder and to subsequent alteration of anatomy. T2*-weighted magnetic resonance imaging (MRI) in the midsagittal plane permitted an analysis of aqueductal CSF flow phenomena and hydrocephalus-induced elevation, thinning and dorsal impingement of the corpus callosum. Furthermore, the width of the third ventricle was measured on the transverse scout images. 72 patients with communicating hydrocephalus (increased aqueductal CSF pulsations) and 26 patients with aqueductal stenosis (absence of aqueductal flow phenomena) were compared with 22 controls. Dementia and affective disorders were distributed equally among both CSF flow subgroups whereas pseudo-neurasthenic syndromes were observed more frequently in non-communicating hydrocephalus (p < 0.03). Alzheimer-type and multiinfarct dementia syndromes were found more frequently in communicating hydrocephalus whereas non-classifiable dementia showed some predilection for non-communicating hydrocephalus. Callosal height, area and third ventricular width did not predict affective or pseudoneurasthenic disorder whereas third ventricular width (p < 0.01) and callosal area (p < 0.05) discriminated between demented and non-demented patients. Dorsal impingement of the corpus callosum by the falx was a non-specific finding.

Cerebral Aqueduct