Showing papers by "University of Zurich published in 1992"
TL;DR: It is now feasible to determine whether mice devoid of PrPc can propagate prions and are susceptible to scrapie pathogenesis.
Abstract: PrPC is a host protein anchored to the outer surface of neurons and to a lesser extent of lymphocytes and other cells. The transmissible agent (prion) responsible for scrapie is believed to be a modified form of PrPC. Mice homozygous for disrupted PrP genes have been generated. Surprisingly, they develop and behave normally for at least seven months, and no immunological defects are apparent. It is now feasible to determine whether mice devoid of PrPC can propagate prions and are susceptible to scrapie pathogenesis.
1,688 citations
TL;DR: The objective of the present experiment was to study lesions in the peri-implant and periodontal tissues resulting from ligature placement and subgingival plaque formation in beagle dogs and revealed that clinical and radiographic signs of tissue destruction were more pronounced at implants than at teeth.
Abstract: The objective of the present experiment was to study lesions in the peri-implant and periodontal tissues resulting from ligature placement and subgingival plaque formation. The experiment was performed in 5 beagle dogs which at the start of the study were about 15 months old. They were given a diet which allowed gross plaque formation. The mandibular right premolars were extracted, 3 fixtures (a.m. Branemark) installed and abutment connection performed. Towards the end of a 6-month plaque control period, a clinical and radiographic examination was performed. Ligatures were placed in a subgingival position at 2 of the implants and the contralateral premolars. Plaque was allowed to accumulate. After 6 weeks, the ligatures were removed. 1 month later, the clinical and radiographical examination was repeated and samples from the subgingival microbiota obtained. Biopsies from the teeth and implant sites were harvested and processed for histometric and morphometric analyses. The results from the clinical and histological examinations revealed that: (i) clinical and radiographic signs of tissue destruction were more pronounced at implants than at teeth; (ii) the size of the soft tissue lesion was larger at implants than at teeth; (iii) the lesion at implants but not at teeth extended into the bone marrow.
616 citations
TL;DR: DPCPX increased the rate of spontaneous bursting, consistent with a tonic activation of adenosine receptors during hyperactivity, and led to the development of prolonged ictal‐like bursts, suggesting that the endogenous release ofadenosine may contribute to the termination of epileptic bursts.
Abstract: 1. Intracellular microelectrode recordings were used to study the cellular location, the receptor pharmacology, and the mechanism of action of adenosine on pyramidal cells and presynaptic axonal endings in area CA3 of organotypic hippocampal slice cultures. 2. Adenosine (bath applied at 50 microM) caused a 10-15 mV hyperpolarization of CA3 cells, as well as a 75-100% decrease in the amplitude of excitatory and polysynaptic inhibitory postsynaptic potentials (EPSPs and IPSPs). Adenosine had no effect on the amplitude of monosynaptic IPSPs elicited in the presence of excitatory amino acid receptor antagonists, but did reduce the amplitude of isolated EPSPs, elicited after blocking GABAA receptors and reducing subsequent epileptic bursts with excitatory amino acid receptor antagonists. These data indicate that adenosine receptors are located on excitatory, but not inhibitory, presynaptic elements. 3. The A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, bath applied at 200 nM) blocked the pre- and postsynaptic actions of adenosine. DPCPX had no effect on the amplitude of control synaptic responses, suggesting that there is no tonic activation of adenosine receptors in hippocampal slice cultures under control conditions. The A1 receptor agonists R-N6-phenylisopropyladenosine (R-PIA) mimicked all pre- and postsynaptic actions of adenosine. 4. Pertussis toxin pretreatment (500 ng/ml for 48 h) prevented adenosine from activating postsynaptic K+ conductance, but not from inhibiting EPSPs. In contrast, stimulation of protein kinase C with phorbol ester (phorbol 12, 13-dibutyrate, 1 microM for 10 min) reduced the presynaptic, but not the postsynaptic, actions of adenosine. 5. Barium (bath applied at 1 mM) blocked the adenosine-activated K+ conductance, but not the inhibition of isolated EPSPs by adenosine. 6. Adenosine at 0.03-1 microM reduced the frequency of, or blocked, spontaneous epileptiform bursting produced by bicuculline. DPCPX (200 nM) increased the rate of spontaneous bursting, consistent with a tonic activation of adenosine receptors during hyperactivity, and led to the development of prolonged ictal-like bursts, suggesting that the endogenous release of adenosine may contribute to the termination of epileptic bursts. 7. We conclude that adenosine acts at pre- and postsynaptic receptors which are pharmacologically indistinguishable. Postsynaptically, adenosine increases a barium-sensitive K+ conductance via a pertussis toxin-sensitive GTP-binding protein. The presynaptic action of adenosine must, however, be mediated by some other mechanism.
475 citations
TL;DR: Among women, a diagnosis of depression was more often associated with disturbances of appetite and with phobias than among men, and when syndromes or diagnoses were controlled, women and men suffered to an equal rate from subjective impairment at work.
Abstract: The purpose of this study was to investigate antecedents of first incidence of major depressive disorder and recurrent brief depression with the help of a cohort of 20 year-old Swiss, who was interviewed four times up to age 30. Cases diagnosed as depressed at the third or fourth interview (age 28 or 30) were compared with never diagnosed controls for antecedents at the first and second interview (age 21 and 23). Besides retrospectively assessed childhood precursors, later depressives showed slight differences in their relationship to parents and friends and early symptoms of subclinical depression, persistent helplessness and a surplus of life events. These antecedents were mainly found in females. The most persistent antecedent of later depression for both sexes was a higher score than controls' on the SCL-90R (“negative affectivity”). Whether this finding signifies that proneness to the milder depressions in young adults is rooted in personality is subject to discussion.
454 citations
TL;DR: Data from the prospective Zurich Study with four interviews over 10 years give relatively high 10-year prevalence rates for subjects from age 20 to 30, and it has to be assumed that lifetime prevalence rates based on recall may greatly underestimate true morbidity.
Abstract: Review of the published literature produces 1-year prevalence rates for major depressive disorder DSM-III between 2.6 and 6.2%, for dysthymia between 2.3 and 3.7%, bipolar disorder 1.0-1.7%. Data from the prospective Zurich Study with four interviews over 10 years give relatively high 10-year prevalence rates for subjects from age 20 to 30 (14.4% major depression, 10.5% recurrent brief depression, 0.9% dysthymia, 3.3% bipolar disorder, 1.3% hypomania). On average, 49% of all these cases received treatment for affective disorder, resulting in a weighted treatment prevalence rate of the population of 11.6% (18% for females and 5% for males). It has to be assumed that lifetime prevalence rates based on recall may greatly underestimate true morbidity.
416 citations
TL;DR: The detection and quantification of Ca(2+)-binding proteins and the neuron populations in which they occur may nevertheless be useful to estimate, for example, the location and extent of brain damage in the various neurological disorders.
404 citations
TL;DR: The mucosa around implants and the gingiva around teeth had a similar potential to respond to early plaque formation and both responded to de novo plaque formation with the development of an inflammatory lesion.
Abstract: The aim of the present investigation was to assess the effect of de novo plaque formation on the gingiva and masticatory mucosa around teeth and implants. The study was performed in 5 beagle dogs which at the initiation of the experiment were 15 months old. During a preparatory period, the mandibular right premolars were extracted, 3 fixtures installed, abutment connection performed and a 4-month period of plaque control completed. A clinical examination was performed and biopsies of the second mandibular premolar (P2) and the contralateral implant site (2P) were sampled. The dogs were allowed to form plaque during a period of 3 weeks. The clinical examination was repeated and biopsies harvested from the 2 remaining implants and the contralateral tooth sites. The tissue samples were prepared for histometric and morphometric analysis. Both the masticatory mucosa at implants and the gingiva responded to de novo plaque formation with the development of an inflammatory lesion. The size as well as the composition of the lesions in the 2 tissues had many features in common. It was concluded that the mucosa around implants and the gingiva around teeth had a similar potential to respond to early plaque formation.
401 citations
TL;DR: Cd2+ blocked evoked synaptic transmission, but had no effect on the frequency or amplitude of either mEPSCs or inhibitory postsynaptic currents (IPSCs), and inhibition of presynaptic Ca2+ current appears not to be required for the inhibition of glutamate release by adenosine and baclofen.
373 citations
TL;DR: It is found that expanded (CAG)n alleles undergo alteration in length when transmitted from parent to offspring, and there was a greater rate of instability in male meiosis than in female meiosis.
Abstract: Expansion of the trinucleotide repeat (CAG)n in the first exon of the androgen receptor gene is associated with a rare motor neuron disorder, X-linked spinal and bulbar muscular atrophy. We have found that expanded (CAG)n alleles undergo alteration in length when transmitted from parent to offspring. Of 45 meioses examined, 12 (27%) demonstrated a change in CAG repeat number. Both expansions and contractions were observed, although their magnitude was small. There was a greater rate of instability in male meiosis than in female meiosis. We also found evidence for a correlation between disease severity and CAG repeat length, but other factors seem to contribute to the phenotypic variability in this disorder.
370 citations
Journal Article•
TL;DR: Provided production and activation of latent TGF-beta occur in vivo, astrocytes and microglia may then be expected to exert regulatory influences on immune mediated diseases of the central nervous system.
Abstract: The type beta transforming growth factors (TGF) are potent regulators of the growth and functions of lymphocytes and macrophages. Recently the human glioblastoma cell line 308 was shown to produce TGF-beta 2. The relevance of this finding was evaluated further by comparing human glioblastoma cells with their nontransformed animal counterpart, astrocytes, with regard to the production of the three TGF-beta isoforms observed so far in mammals. In this report astrocytes are demonstrated to secrete also TGF-beta 2 and to express TGF-beta 1, -beta 2, and -beta 3 mRNA in vitro. In contrast, cultured murine brain macrophages release TGF-beta 1 and are positive for TGF-beta 1 mRNA only. Glia cell-derived TGF-beta 1 and -beta 2 are detected in latent form whereas both latent and active TGF-beta are identified in the supernatant of three human glioblastoma cell lines tested. These cell lines, however, show heterogeneity in regard to the isoform of TGF-beta expressed but share with astrocytes the inability to release TGF-beta 3. Provided production and activation of latent TGF-beta occur in vivo, astrocytes and microglia may then be expected to exert regulatory influences on immune mediated diseases of the central nervous system.
365 citations
TL;DR: To identify receptor subtypes in situ, the most prevalent subunits were visualized by double and triple immunofluorescence staining in rat brain, and different subunits displayed the same local variations of staining intensity ("hot spots") along the plasma membrane.
Abstract: The extraordinary structural diversity of subunits forming type A gamma-aminobutyric acid (GABAA) receptors in the brain is expected to give rise to different modes of GABAergic synaptic inhibition and different profiles of modulatory drugs effective in anxiolytic, hypnotic, and antiepileptic therapy To identify receptor subtypes in situ, the most prevalent subunits were visualized by double and triple immunofluorescence staining in rat brain, using polyclonal antibodies to the alpha 1, alpha 3, and gamma 2 subunits and a monoclonal antibody to locate both the beta 2 and the beta 3 subunit At both cellular and subcellular levels five distinct patterns of subunit colocalization were identified: I, alpha 1 beta 2,3 gamma 2; II, alpha 3 beta 2,3 gamma 2; III, alpha 1 alpha 3 beta 2,3 gamma 2; IV, alpha 3 gamma 2; and V, alpha 1 alpha 3 gamma 2 As analyzed by confocal laser microscopy, different subunits displayed the same local variations of staining intensity ("hot spots") along the plasma membrane The covisualized subunits appear therefore to be coassembled in receptor subtypes Most neurons expressed only a single major receptor subtype with no apparent distinction between synaptic and extrasynaptic sites However, in some neurons, most notably in Purkinje cells, the subunit composition varied between the soma and the dendrites, pointing to the existence of receptor heterogeneity within single neurons Furthermore, different populations of neurons may be characterized by particular receptor subtypes Cells displaying alpha 1-subunit immunoreactivity were mostly identified as GABAergic, whereas monoaminergic neurons displayed intense alpha 3-subunit immunoreactivity but virtually no alpha 1-subunit immunoreactivity The allocation of defined GABAA receptor subtypes to identified neurons opens the way for a functional analysis of receptor heterogeneity
TL;DR: A larger set of transcription factors is examined with respect to their proximal versus remote activation, and at least two distinct functional classes of transcriptional activation domains are identified.
Abstract: We reported previously that the lymphocyte-derived octamer transcription factor 2A (Oct-2A or OTF-2A) activated both natural immunoglobulin promoters and synthetic promoters which contain the 'octamer' site, but was unable by itself to stimulate transcription from a remote enhancer position. Here we examine a larger set of transcription factors with respect to their proximal versus remote activation. Since a transcription factor may contain more than one activation domain, we have chosen to study the potential of individual activation domains in the context of fusion proteins that contain the DNA binding domain of GALA. We have identified at least two distinct functional classes of transcriptional activation domains. 'Proximal' activation domains, exemplified by glutamine-rich domains of Oct-1, Oct-2A and Sp1, stimulate transcription only from a position close to the TATA box, usually in response to a remote enhancer. 'General' activation domains, derived from VP16, GAL4, p65 (NF-chi B), TFE3, ITF-1 and ITF-2, can activate transcription from remote as well as proximal positions. These domains contain many acidic amino acids and/or other features such as clusters of serine and threonine. The proline-rich activation domains of AP-2 and CTF/NF1 may represent a third class with considerable promoter activity and low but significant enhancer activity. Furthermore, activation domains of both the acidic and glutamine-rich types seem to have a modular structure, since duplicated subdomains can substitute for the entire domain.
TL;DR: It is shown that the Drosophila Raf serine/threonine kinase also plays a crucial role in the R7 pathway: the response to Sev activity is dependent on raf function, and a constitutively activated Raf protein can induce R7 cell development in the absence of sev function.
Abstract: SPECIFICATION of the R7 cell fate in the developing Drosophila eye requires activation of the Sevenless (Sev) receptor tyrosine kinase, located on the surface of the R7 precursor cell, by its interaction with the Boss protein, expressed on the surface of the neighbouring R8 cell1–3 Four genes that participate in the intracellular transmission of this signal have so far been identified and molecularly characterized: Rasl, Sos, Gapl and sina (refs 4–8) The Drosophila homologue of the mammalian Raf-1 serine/threonine kinase, which has been implicated in signal transduction pathways activated by many receptor tyrosine kinases (reviewed in refs 9 and 10), is encoded by the raf locus (also known as l(l)polehole11, Draf-112 or Draf13) Here we show that the Drosophila Raf serine/threonine kinase also plays a crucial role in the R7 pathway: the response to Sev activity is dependent on raf function, and a constitutively activated Raf protein can induce R7 cell development in the absence of sev function We also present genetic evidence suggesting that Raf acts downstream of Rasl and upstream of Sina in this signal transduction cascade
TL;DR: While S- and C-operators are optimised for the representation of 1-D features such as edges and lines, the end-stopped operator responses at the key-points make explicit 2-D signal variations such as line ends, corners and segments of strong curvature.
TL;DR: It is demonstrated that the mouse Mx1 protein interferes with primary transcription of influenza virus in the nucleus, whereas the human MxA protein inhibits a subsequent step that presumably takes place in the cytoplasm of infected cells.
Abstract: Human MxA and mouse Mx1 are interferon-induced proteins capable of inhibiting the multiplication of influenza virus. MxA protein is localized in the cytoplasm, whereas Mx1 protein accumulates in the nucleus. Taking advantage of stably transfected cell lines that constitutively express either MxA or Mx1 protein, we examined the steps at which these proteins block influenza A viruses. In infected cells expressing MxA protein, all viral mRNAs synthesized as a result of primary transcription in the nucleus by the virion-associated RNA polymerase accumulated to normal levels. These primary viral transcripts were polyadenylated, were active in directing viral protein synthesis in vitro, and appeared to be efficiently transported to the cell cytoplasm. Yet viral protein synthesis and genome amplification were strongly inhibited, suggesting that MxA protein interfered with either intracytoplasmic transport of viral mRNAs, viral protein synthesis, or translocation of newly synthesized viral proteins to the cell nucleus. However, in infected cells expressing Mx1 protein, the concentrations of the longest primary transcripts encoding the three influenza virus polymerase proteins PB1, PB2, and PA were at least 50-fold reduced. Accumulation of the shorter primary transcripts encoding the other viral proteins was also inhibited but to a lesser extent. These results demonstrate that the mouse Mx1 protein interferes with primary transcription of influenza virus in the nucleus, whereas the human MxA protein inhibits a subsequent step that presumably takes place in the cytoplasm of infected cells.
Journal Article•
TL;DR: The results show that p53 mutations are not restricted to glioblastoma multiforme and may be important in the tumorigenesis of lower-grade astrocytomas and that p 53 mutations in lower- grade astroCytomas are associated with loss of chromosome 17p.
Abstract: Loss of genetic material on the short arm of chromosome 17 is observed in approximately 40% of human astrocytomas (WHO grades II and III) and in approximately 30% of cases of glioblastoma multiforme (WHO grade IV). Previous studies of glioblastoma multiforme have shown that the p53 gene, located on the short arm of chromosome 17, is frequently mutated in these glioblastomas. To explore whether lower-grade astrocytomas are also associated with corresponding mutations of the p53 gene, we have investigated a series of 22 human astrocytomas of WHO grades II and III both for loss of heterozygosity on chromosome 17p and for p53 mutations. Mutations in the conserved regions of the p53 gene were identified by single strand conformation polymorphism analysis of exons 5, 6, 7, and 8 and were verified by direct DNA sequencing of the polymerase chain reaction products. p53 mutations were observed in 3 of 8 grade II astrocytomas and 4 of 14 grade II astrocytomas. In all 22 tumors, allelic loss of the short arm of chromosome 17 was investigated by restriction fragment length polymorphism analysis. One-half of the grade II astrocytomas (4 of 8) and grade III astrocytomas (7 of 14) exhibited allelic loss on chromosome 17p. Mutations in the p53 gene were exclusively observed in tumors with allelic loss on 17p. Our results show that p53 mutations are not restricted to glioblastoma multiforme and may be important in the tumorigenesis of lower-grade astrocytomas and that p53 mutations in lower-grade astrocytomas are associated with loss of chromosome 17p. These findings are consistent with a recessive mechanism of action of p53 in WHO grade II and III astrocytoma tumorigenesis.
TL;DR: histological examination of the gingiva and the peri-implant mucosa revealed: (i) both tissues contained an inflammatory cell infiltrate; ICT, (ii) the apical extension of ICT was more pronounced in the peringiva than in theGingiva, and (iii) the composition of the 2 lesions had many features in common.
Abstract: The experiment was performed to evaluate the effects of long-standing plaque on the gingiva and peri-implant mucosa. 5 beagle dogs were used in the study. The mandibular right premolars were extracted. 3 months later, 3 titanium fixtures were installed and after another 3 months, abutment connection was performed. Plaque control, in the implant as well as the contralateral tooth regions, was maintained during a 4-month period prior to the start of the main experiment. On Day 0, the teeth and implant sections were examined with respect to plaque and gingivitis. The plaque control program was terminated. The animals were subsequently fed a diet which allowed gross plaque accumulation. After 90 days of undisturbed plaque formation, the dogs were re-examined and biopsies harvested from implants and contralateral teeth. On day 90, all teeth and implants had accumulated large amounts of plaque. The soft tissue at implants and teeth bled on gentle probing. The histological examination of the gingiva and the peri-implant mucosa revealed: (i) both tissues contained an inflammatory cell infiltrate; ICT, (ii) the apical extension of ICT was more pronounced in the peri-implant mucosa than in the gingiva and (iii) the composition of the 2 lesions had many features in common.
TL;DR: Brain macrophages termed microglial cells co‐cultured with differentiated cerebellar neurons excert potent neurotoxic effects and dibenzocyclohepteneimide, an antagonist to NMDA receptors neutralized neurotoxicity in microglia‐neuronal co‐culture are suggested to compose the major determinant of neurotoxicity.
Abstract: The co-localization of activated macrophages and damaged neurons observed in brain injury and degenerative brain diseases may hint to macrophage-induced neuronal cytotoxicity. Recently, macrophages have been found to secrete neurotoxic molecules such as radical oxygen intermediates and glutamate, the latter interacting with N-methyl-D-aspartate (NMDA) receptors. As shown in the present study, brain macrophages termed microglial cells co-cultured with differentiated cerebellar neurons excert potent neurotoxic effects. Neurotoxicity is unlikely to be due to cytokines since tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6 and interferon (IFN)-alpha/IFN-beta/IFN-gamma had no such effects. In contrast, when treating neurons with H2O2 or oxygen radical-generating systems cytotoxicity was induced. Furthermore, microglia were found to produce O2- and H2O2 when triggered with phorbol 12-myristate 13-acetate. However, in co-cultures of neurons and microglia, oxygen-radical scavengers catalase and superoxide dismutase, failed to protect neurons from microglia-induced killing. Moreover, when using undifferentiated neurons which are susceptible to H2O2 but not to NMDA receptor-dependent killing, microglia did not destroy the neurons. Thus, the amount of reactive oxygen intermediates produced by microglia in co-culture do not reach the critical concentrations required for neurotoxicity. As dibenzocyclohepteneimide, an antagonist to NMDA receptors neutralized neurotoxicity in microglia-neuronal co-cultures, excitatory amino acids released by microglia are suggested to compose the major determinant of neurotoxicity.
Journal Article•
TL;DR: A novel mechanism which allows in vitro or in vivo primed eosinophils to leave the vascular compartment without influencing emigration of neutrophils is demonstrated.
Abstract: The mechanism leading to selective accumulation of eosinophils in allergic inflamed tissue is still unknown. In this article, transendothelial migration of circulating eosinophils from normal and allergic individuals is characterized by means of human umbilical vein endothelial cells cultivated on extracellular matrix from human fibroblasts. IL-4 pretreatment of these vascular constructs induced adherence and impressive layer penetration of eosinophils but not of neutrophils. For layer penetration, blood eosinophils from nonallergic donors needed in vitro priming by granulocyte/macrophage-CSF, IL-3, or IL-5. In contrast, freshly isolated blood eosinophils from a group of patients with atopic dermatitis spontaneously penetrated IL-4-activated vascular constructs. The here described selective pathway of eosinophil transmigration was 1) specifically induced by IL-4; 2) inhibited by the IL-4 specific, neutralizing mAb 8F12; and 3) dependent upon endothelial mRNA synthesis. Both eosinophil adherence and transmigration were present at an IL-4 concentration of 1 U/ml. The effect of endothelial preincubation with IL-4 culminated at 16 h and persisted up to 48 h. A linear increase of subendothelial accumulating eosinophils was observed within 2 h, reaching almost 100% after 4 h of coincubation. From inhibition experiments using different mAb, we conclude that the integrins CD11a/CD18, CD11b/CD18, and very late Ag-4 (CDw49d/CD29) are involved in this selective pathway of eosinophil transmigration. Taken together, this study demonstrates a novel mechanism which allows in vitro or in vivo primed eosinophils to leave the vascular compartment without influencing emigration of neutrophils.
TL;DR: The gene encoding the small nuclear RNA associated polypeptide SmN (SNRPN) to human chromosome 15q12 and a processed pseudogene SNRPNP1 to chromosome region 6pter–p21 was mapped to the minimal deletion interval that is critical for PWS.
Abstract: Prader-Willi syndrome (PWS) is associated with paternally derived chromosomal deletions in region 15q11-13 or with maternal disomy for chromosome 15. Therefore, loss of the expressed paternal alleles of maternally imprinted genes must be responsible for the PWS phenotype. We have mapped the gene encoding the small nuclear RNA associated polypeptide SmN (SNRPN) to human chromosome 15q12 and a processed pseudogene SNRPNP1 to chromosome region 6pter-p21. Furthermore, SNRPN was mapped to the minimal deletion interval that is critical for PWS. The fact that the mouse Snrpn gene is maternally imprinted in brain suggests that loss of the paternally derived SNRPN allele may be involved in the PWS phenotype.
15 Sep 1992-Nuclear Instruments & Methods in Physics Research Section A-accelerators Spectrometers Detectors and Associated Equipment
TL;DR: In this paper, the crystal Barrel spectrometer used at LEAR, CERN to study the products of pd annihilations is described and the performance of the detector is discussed.
Abstract: The crystal Barrel spectrometer used at LEAR, CERN to study the products of pd annihilations is described. A 1380 element array of Csl crystals measures photons from the decay of π0, η, η′ and ω mesons. A segmented drift chamber in a 1.5T magnetic field is used to identify and measure charged particles. A fast on-line trigger on charged and neutral multiplicities and on the invariant mass of secondary particles is available. The performance of the detector is discussed.
TL;DR: Both N-CAM and sodium channels carry homopolymers of alpha 2,8-linked polysialic acid in adult rat brain, and evidence that N- CAM is not the only polySia bearing protein in adultRat brain is presented.
TL;DR: Close links have emerged between the processes postulated by the various models and specific brain mechanisms, and the modelling approach has become one of the potent research strategies in sleep science.
Abstract: Various mathematical models have been proposed to account for circadian, ultradian and homeostatic aspects of sleep regulation. Most circadian models assume that multiple oscillators underlie the differences in period and entrainment properties of the sleep/wake cycle and other rhythms (e.g. body temperature). Interactions of the oscillators have been postulated to account for multimodal sleep/wake patterns. The ultradian models simulate the cyclic alternation of nonREM sleep and REM sleep by assuming a reciprocal interaction of two cell groups. The homeostatic models propose that a sleep/wake dependent process (Process S) underlies the rise in sleep pressure during waking and its decay during sleep. The time course of this process has been derived from EEG slow-wave activity, an indicator of nonREM sleep intensity. The predictions of homeostatic models have been most extensively tested in experiments. The interaction of Process S with a single circadian process can account for multimodal sleep/wake patterns, internal desynchronization and the time course of daytime sleepiness. Close links have emerged between the processes postulated by the various models and specific brain mechanisms. Due to its recent quantitative elaboration and experimental validation, the modelling approach has become one of the potent research strategies in sleep science.
TL;DR: In this article, two nuclear enzymes, i.e., poly(ADP-ribose) polymerase (EC 2.4.2.30) and poly (ADP)-ribose glycohydrolase, may cooperate to function as a histone shuttle mechanism on DNA.
TL;DR: It is concluded that GABA uptake plays a significant role in determining the time course of evoked IPSPs and also limits the likelihood that GABAB receptors are activated.
Abstract: 1. The effects of the gamma-aminobutyric acid (GABA) uptake blocker tiagabine on inhibitory synaptic potentials (IPSPs) were examined with microelectrode and whole-cell recording from CA3 pyramidal cells in rat hippocampal slice cultures. 2. Tiagabine (10-25 microM) greatly prolonged the duration of monosynaptic IPSPs elicited in the presence of excitatory amino acid antagonists but had no effect on their amplitude. Part of the prolonged time course resulted from a GABAB receptor-mediated component that was not detectable under control conditions. 3. The mean decay time constant of the underlying GABAA receptor-mediated synaptic current was increased from 16 to 250 ms. Spontaneous miniature IPSPs recorded with whole-cell clamp were unaffected by tiagabine. Pentobarbital sodium, in contrast, increased the decay time constant of both evoked and spontaneous GABAA-mediated currents. 4. Tiagabine (25 microM) inhibited spontaneous and evoked epileptiform bursting induced by increasing the extracellular potassium concentration to 8 mM. 5. We conclude that GABA uptake plays a significant role in determining the time course of evoked IPSPs and also limits the likelihood that GABAB receptors are activated.
Journal Article•
TL;DR: Genetic similarities between astrocytomas, oligodendrogliomas, and mixed glial tumors are demonstrated and the presence of a glial tumor suppressor gene on chromosome 19q is indicated.
Abstract: Previous studies have shown frequent allelic losses of chromosomes 9p, 10, 17p, and 22q in glial tumors. Other researchers have briefly reported that glial tumors may also show allelic losses of chromosome 19, suggesting a putative tumor suppressor gene locus on this chromosome (D. T. Ransom et al. , Proc. Am. Assoc. Cancer Res., 32: 302, 1991). To evaluate whether loss of chromosome 19 alleles is common in glial tumors of different types and grades, we performed Southern blot restriction fragment length polymorphism analysis for multiple chromosome 19 loci in 122 gliomas from 116 patients. Twenty-nine tumors had loss of constitutional heterozygosity of 19q, and four tumors had partial deletions of 19q. Allelic losses on 19q were restricted to grade III anaplastic astrocytomas (4/9) and grade IV glioblastomas (11/46), grade II oligodendrogliomas (2/5) and grade III anaplastic oligodendrogliomas (2/2), and grade II (5/8) and grade III (5/7) mixed oligoastrocytomas. These data demonstrate genetic similarities between astrocytomas, oligodendrogliomas, and mixed glial tumors and indicate the presence of a glial tumor suppressor gene on chromosome 19q.
Journal Article•
TL;DR: The flexural strength of a new heat-pressed ceramic material (IPS-Empress) was measured before and after pressing and/or simulated firing treatments (eg, veneering, surface coloring, glazing) and were comparable to some other all-ceramic systems.
Abstract: The flexural strength of a new heat-pressed ceramic material (IPS-Empress) was measured before and after pressing and/or simulated firing treatments (eg, veneering, surface coloring, glazing). Heat pressing the material significantly improved its flexure strength whereas heat treating the material alone did not. Additional firings (heat treatments) after heat pressing further increased material strength. The final strength values ranged between 160 and 180 MPa and were comparable to some other all-ceramic systems. No clinical implications were drawn from these data.
TL;DR: The Saharan silver ant Cataglyphis bombycina is exceptional in that all foragers leave their underground nest in an explosive outburst confined to a few minutes per day during the hottest midday period.
Abstract: MANY animals restrict their foraging activities to certain times of the day or night, but the Saharan silver ant Cataglyphis bombycina is exceptional in that all foragers leave their underground nest in an explosive outburst confined to a few minutes per day during the hottest midday period. The foraging activity of this 'thermophilic' ant is compressed into a small thermal window by predatory pressure on the one hand and heat stress on the other.
TL;DR: Observations of anaplastic variants of this neoplasm in two cases and local tumor recurrences in three indicate that the biological behavior and postoperative prognosis of central neurocytoma may not always be as favorable as previously assumed.
Abstract: ✓ The central neurocytoma has recently been added to the differential diagnosis of intraventricular tumors. Histopathologically, this tumor is characterized by a uniform neoplastic cell population with features of neuronal differentiation. Central neurocytomas occur in young adults, develop in the area of the foramen of Monro, and are usually associated with the septum pellucidum. Initial reports appeared to indicate that these tumors are benign lesions with a favorable postoperative prognosis. The authors present clinical and neuropathological findings in a series of eight patients with central neurocytoma. An anterior transcallosal microneurosurgical approach yielded good outcomes. Postoperative radiation therapy was restricted to two patients with a malignant variant of central neurocytoma and one patient with a recurrent tumor. Observations of anaplastic variants of this neoplasm in two cases and local tumor recurrences in three indicate that the biological behavior and postoperative prognosis of cent...
TL;DR: The nucleotide sequence of the two highly homologous genes encoding 3β–HSD isoenzymes in three classic 3β-HSD deficient patients belonging to two apparently unrelated pedigrees is described, providing the first elucidation of the molecular basis of this disorder.
Abstract: Classical 3β–hydroxysteroid dehydrogenase /Δ5–Δ4–isomerase (3β–HSD) deficiency is an autosomal recessive form of congenital adrenal hyperplasia characterized by a severe impairment of steroid biosynthesis in both the adrenals and the gonads We describe the nucleotide sequence of the two highly homologous genes encoding 3β–HSD isoenzymes in three classic 3β–HSD deficient patients belonging to two apparently unrelated pedigrees No mutation was detected in the type I 3β–HSD gene, which is mainly expressed in the placenta and peripheral tissues Both nonsense and frameshift mutations, however, were found in the type II 3β–HSD gene, which is the predominant 3β–HSD gene expressed in the adrenals and gonads, thus providing the first elucidation of the molecular basis of this disorder