Showing papers by "University of Düsseldorf published in 1999"
TL;DR: This article serves as introduction to the FRBM Forum on glutathione and emphasizes cellular functions: What is GSH?
1,607 citations
TL;DR: These morphologic asymmetries of area 44 provide a putative correlate of the functional lateralization of speech production and show that macroscopic features are not reliable landmarks of cytoarchitectonic borders.
Abstract: The sizes of Brodmann's areas 44 and 45 (Broca's speech region) and their extent in relation to macroscopic landmarks and surrounding areas differ considerably among the available cytoarchitectonic maps. Such variability may be due to intersubject differences in anatomy, observer-dependent discrepancies in cytoarchitectonic mapping, or both. Because a reliable definition of cytoarchitectonic borders is important for interpreting functional imaging data, we mapped areas 44 and 45 by means of an observer-independent technique. In 10 human brains, the laminar distributions of cell densities were measured vertical to the cortical surface in serial coronal sections stained for perikarya. Thousands of density profiles were obtained. Cytoarchitectonic borders were defined as statistically significant changes in laminar patterns. The analysis of the three-dimensional reconstructed brains and the two areas showed that cytoarchitectonic borders did not consistently coincide with sulcal contours. Therefore, macroscopic features are not reliable landmarks of cytoarchitectonic borders. Intersubject variability in the cytoarchitecture of areas 44 and 45 was significantly greater than cytoarchitectonic differences between these areas in individual brains. Although the volumes of area 44 differed across subjects by up to a factor of 10, area 44 but not area 45 was left-over-right asymmetrical in all brains. All five male but only three of five female brains had significantly higher cell densities on the left than on the right side. Such hemispheric and gender differences were not detected in area 45. These morphologic asymmetries of area 44 provide a putative correlate of the functional lateralization of speech production. J. Comp. Neurol. 412:319–341, 1999. © 1999 Wiley-Liss, Inc.
1,272 citations
TL;DR: It is suggested that a fronto‐parietal circuit for manipulation of objects exists in humans and involves basically the same areas as in the monkey and it is proposed that area SII analyses the intrinsic object characteristics whilst the superior parietal lobule is related to kinaesthesia.
Abstract: Functional magnetic resonance imaging (fMRI) was used to localize brain areas active during manipulation of complex objects. In one experiment subjects were required to manipulate complex objects for exploring their macrogeometric features as compared to manipulation of a simple smooth object (a sphere). In a second experiment subjects were asked to manipulate complex objects and to silently name them upon recognition as compared to manipulation of complex not recognizable objects without covert naming. Manipulation of complex objects resulted in an activation of ventral premotor cortex [Brodmann's area (BA) 44], of a region in the intraparietal sulcus (most probably corresponding to the anterior intraparietal area in the monkey), of area SII and of a sector of the superior parietal lobule. When the objects were covertly named additional activations were found in the opercular part of BA 44 and in the pars triangularis of the inferior frontal gyrus (BA 45). We suggest that a fronto-parietal circuit for manipulation of objects exists in humans and involves basically the same areas as in the monkey. It is proposed that area SII analyses the intrinsic object characteristics whilst the superior parietal lobule is related to kinaesthesia.
728 citations
TL;DR: There is increasing evidence that microglia play an active part in degenerative CNS diseases, in Alzheimer's disease activated microglian appear to be involved in plaque formation, and in experimental globoid cell dystrophy T-cell independent induction of major histocompatibility complex class II molecules on microglio accelerates demyelination.
679 citations
Journal Article•
TL;DR: It is demonstrated that COX-2 is expressed in the majority of esophageal SCCs and ADCs and that COx-2-derived PGs play an important role in the regulation of proliferation and apoptosis of esphageal tumor cells.
Abstract: On the basis of epidemiological observations that nonsteroidal anti-inflammatory drugs reduce the risk of esophageal carcinoma, we studied the expression of cyclooxygenase-2 (COX-2) in esophageal squamous cell carcinomas (SCCs; n = 172) and in esophageal adenocarcinomas (ADCs; n = 27). Using immunohistochemistry, we observed COX-2 expression in 91% of the SCCs and in 78% of the ADCs. Western blot analysis showed enhanced expression of the COX-2 protein in some tumors as compared with normal esophageal squamous epithelium, whereas similar amounts of the COX-1 protein were found in normal and cancerous tissues. COX expression was also studied in two esophageal cancer cell lines (OSC-1 and OSC-2) to evaluate the functional relevance of COX-2-derived prostaglandins (PGs). OSC-2 cells expressed COX-2 but not COX-1, whereas OSC-1 cells expressed high levels of COX-1 but showed only a very weak COX-2 expression. Accordingly, PGE2 synthesis was 600 times higher in the OSC-2 cells as compared with the OSC-1 cells. Treatment of OSC-2 cells with the selective COX-2 inhibitors flosulide and NS-398 concentration dependently suppressed PGE2 synthesis and proliferation and also induced apoptosis. In contrast, no effect of the COX-2 inhibitors was seen in OSC-1 cells. Our data demonstrate that COX-2 is expressed in the majority of esophageal SCCs and ADCs and that COX-2-derived PGs play an important role in the regulation of proliferation and apoptosis of esophageal tumor cells. It is concluded that inhibition of COX-2 may be useful in the therapy of esophageal cancer.
675 citations
TL;DR: Increasing knowledge on the complex metabolism of NO in vivo will lead to the development of new therapeutic strategies to enhance bioactivity of NO via modulation of its metabolism.
631 citations
TL;DR: As additional deletion of the glucose sensor gene SNF3 partially restored growth on hexoses, the data indicate the existence of even more proteins able to transport hexoses in yeast.
612 citations
TL;DR: Only patients with severe perfusion deficits in the PWI/DWI mismatch (TTP delays of >/=6 s) are at high risk of lesion enlargement, and Functionally, more moderate perfusions appear to also contribute to the acute clinical deficit.
Abstract: Background and Purpose —Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) are relatively new MR techniques increasingly used in acute stroke. During the first hours of stroke evolution, the regions with abnormal perfusion are typically larger than the DWI lesions, and this mismatch region has been suggested to be “tissue at risk.” The aim of this study was to evaluate the PWI/DWI mismatch region in acute stroke patients and find parameters indicative of both infarct progression and functional impairment. Methods —Twenty patients with nonlacunar ischemic stroke were imaged with DWI, PWI, and conventional MRI within 24 hours of symptom onset and after 1 week; in addition, the European Stroke Scale (ESS) score was recorded. With PWI, the volumes of regions with “time-to-peak” (TTP) delays of ≥2, 4, 6, 8, and 10 seconds were measured; these volumes were compared with the acute DWI lesion volumes, final infarct size, and ESS score. Results —In 80% of patients the acute DWI lesion was surrounded by regions with abnormal TTP delays (PWI>DWI lesion). A TTP delay of ≥6 s in the mismatch region was found to be associated with lesion enlargement between the initial and follow-up MRI scans. Lesions increased in 9 of 12 patients (75%) in whom the area with TTP delay ≥6 s was larger than the DWI lesion, but they increased in only 1 of 8 (12.5%) of the remaining patients, in whom the area with a TTP delay ≥6 s was smaller than the DWI lesion. The volume of the regions with TTP delays of ≥4 s correlated better with ESS ( r =−0.88, P Conclusions —Only patients with severe perfusion deficits in the PWI/DWI mismatch (TTP delays of ≥6 s) are at high risk of lesion enlargement. Functionally, more moderate perfusion deficits (TTP delays ≥4 and
574 citations
TL;DR: It is proposed that RPR, HID, and GRIM promote apoptosis by disrupting productive IAP-caspase interactions and that DIAP1 is required to block apoptosis-inducing caspase activity.
512 citations
Journal Article•
TL;DR: It is shown that autologous hsp60 is also an Ag recognized by cells of the innate immune system, such as macrophages, and induces gene expression of the Th1-promoting cytokines IL-12 and IL-15.
Abstract: Mammalian 60-kDa heat-shock protein (hsp60) is a key target of T cell and Ab responses in chronic inflammation or atherosclerosis. We show in this study that human hsp60 is also an Ag recognized by cells of the innate immune system, such as macrophages. Both mouse and human macrophages respond to contact with exogenous human hsp60 with rapid release of TNF-alpha; mouse macrophages in addition produce nitric oxide. The proinflammatory macrophage response is hsp60 dose dependent and similar in kinetics and extent to LPS stimulation. Human hsp60 was found to synergize with IFN-gamma in its proinflammatory activity. Finally, human hsp60 induces gene expression of the Th1-promoting cytokines IL-12 and IL-15. These findings identify autologous hsp60 as a danger signal for the innate immune system, with important implications for a role of local hsp60 expression/release in chronic Th1-dependent tissue inflammation.
503 citations
TL;DR: Only genuine microstructural analysis can define the borders between these cortical areas, and additional significant borders which do not correlate with visible changes in cytoarchitecture can be found within areas 3b and 1.
TL;DR: Sucrose and its derivatives represent the major transport forms of photosynthetically assimilated carbon in plants and are exported via the phloem, the long-distance distribution network for assimilates.
Abstract: Sucrose and its derivatives represent the major transport forms of photosynthetically assimilated carbon in plants Sucrose synthesized in green leaves is exported via the phloem, the long-distance distribution network for assimilates, to supply nonphotosynthetic organs with energy and carbon
TL;DR: It is proposed that, after delamination of the neuroblast from the neuroepithelium, Bazooka provides an asymmetric cue in the apical cytocortex that is required to anchor Inscuteable, the missing link between epithelial polarity and neuroblast polarity.
Abstract: Asymmetric cell division generates daughter cells with different developmental fates from progenitor cells that contain localized determinants. During this division, the asymmetric localization of cell-fate determinants and the orientation of the mitotic spindle must be precisely coordinated. In Drosophila neuroblasts, inscuteable controls both spindle orientation and the asymmetric localization of the cell-fate determinants Prospero and Numb. Inscuteable itself is localized in an apical cortical crescent and thus reflects the intrinsic asymmetry of the neuroblast. Here we show that localization of Inscuteable depends on Bazooka, a protein containing three PDZ domains with overall sequence similarity to Par-3 of Caenorhabditis elegans. Bazooka and Inscuteable form a complex that also contains Staufen, a protein responsible for the asymmetric localization of prospero messenger RNA. We propose that, after delamination of the neuroblast from the neuroepithelium, Bazooka provides an asymmetric cue in the apical cytocortex that is required to anchor Inscuteable. As Bazooka is also responsible for the maintenance of apical-basal polarity in epithelial tissues, it may be the missing link between epithelial polarity and neuroblast polarity.
TL;DR: In combination, low cultivation temperature and heat shock act synergistically and increased the transformation efficiency by four orders of magnitude to 2.5 × 106 cfu μg−1 xenogeneic DNA.
Abstract: An improved method for the electrotransformation of wild-type Corynebacterium glutamicum (ATCC 13032) is described. The two crucial alterations to previously developed methods are: cultivation of cells used for electrotransformation at 18 degrees C instead of 30 degrees C, and application of a heat shock immediately following electrotransformation. Cells cultivated at sub optimal temperature have a 100-fold improved transformation efficiency (10(8) cfu micrograms-1) for syngeneic DNA (DNA isolated from the same species). A heat shock applied to these cells following electroporation improved the transformation efficiency for xenogeneic DNA (DNA isolated from a different species). In combination, low cultivation temperature and heat shock act synergistically and increased the transformation efficiency by four orders of magnitude to 2.5 x 10(6) cfu micrograms-1 xenogeneic DNA. The method was used to generate gene disruptions in C. glutamicum.
TL;DR: The findings accord with the hypothesis that early infection may protect against allergies in later life.
TL;DR: Hereditary non-polyposis colorectal cancer was shown to be caused by germline mutations in the DNA mismatch repair genes MSH2, MLH1, PMS1,PMS2 and MSH6, and many HNPCC families do not fully comply with the clinical Amsterdam criteria, and the causative mutations are unknown.
Abstract: Hereditary non-polyposis colorectal cancer (HNPCC) is a common autosomal dominant condition characterized by early onset colorectal cancer as well as other tumour types at different anatomical sites1. HNPCC tumours often display a high level of genomic instability, characterized by changes in repeat numbers of simple repetitive sequences (microsatellite instability, MSI), which reflects the malfunction of the DNA mismatch repair machinery2, 3. Accordingly, HNPCC was shown to be caused by germline mutations in the DNA mismatch repair genes (MMR) MSH2, MLH1, PMS1, PMS2 and MSH6 (refs 3, 4, 5, 6). So far, more than 220 predisposing mutations have been identified, most in MSH2 and MLH1 and in families complying with the clinical Amsterdam criteria3, 7, 8 (AMS+). Many HNPCC families, however, do not fully comply with these criteria, and in most cases the causative mutations are unknown.
TL;DR: An extended right hemisphere network including frontal (anterior cingulate-dorsolateral cortical)-inferior parietal-thalamic and brainstem (ponto-mesencephalic tegmentum) structures was found when subjects waited for and rapidly responded to a centrally presented white dot by pressing a response key with the right-hand thumb.
TL;DR: Findings indicate that a 3-week intravenous treatment with alpha-lipoic acid, followed by a 6-month oral treatment, had no effect on neuropathic symptoms distinguishable from placebo to a clinically meaningful degree, possibly due to increasing intercenter variability in symptom scoring during the study.
Abstract: OBJECTIVE: To evaluate the efficacy and safety of alpha-lipoic acid given intravenously, followed by oral treatment in type 2 diabetic patients with symptomatic polyneuropathy RESEARCH DESIGN AND METHODS: In a multicenter randomized double-blind placebo-controlled trial (Alpha-Lipoic Acid in Diabetic Neuropathy [ALADIN] III Study), 509 outpatients were randomly assigned to sequential treatment with 600 mg alpha-lipoic acid once daily intravenously for 3 weeks, followed by 600 mg alpha-lipoic acid three times a day orally for 6 months (A-A; n = 167); 600 mg alpha-lipoic acid once daily intravenously for 3 weeks, followed by placebo three times a day orally for 6 months (A-P; n = 174); and placebo once daily intravenously for 3 weeks, followed by placebo three times a day orally for 6 months (P-P; n = 168) Outcome measures included the Total Symptom Score (TSS) for neuropathic symptoms (pain, burning, paresthesias, and numbness) in the feet, and the Neuropathy Impairment Score (NIS) Data analysis was based on the intention to treat RESULTS: No significant differences between the groups were noted for the demographic variables and the nerve function parameters at baseline The TSS in the feet decreased from baseline to day 19 (median [range]) by -37 (-126 to 50) points in the group given alpha-lipoic acid intravenously and by -30 (-123 to 80) points in the placebo group (P = 0447), but the area under curve on a daily basis was significantly smaller in the active as compared with the placebo group (856 [0-219] vs 959 [55-220]); P = 0033) After 7 months, the changes in the TSS from baseline were not significantly different between the three groups studied, which could be due to increasing intercenter variability in the TSS during the trial The NIS decreased after 19 days by -434+/-035 points (mean +/- SEM) in A-A and A-P and -349+/-058 points in P-P (P = 002 for alpha-lipoic acid versus placebo) and after 7 months by -582+/-073 points in A-A, -576+/-069 points in A-P, and -437+/-083 points in P-P (P = 009 for A-A vs P-P) The rates of adverse events were not different between the groups throughout the study CONCLUSIONS: These findings indicate that a 3-week intravenous treatment with alpha-lipoic acid, followed by a 6-month oral treatment, had no effect on neuropathic symptoms distinguishable from placebo to a clinically meaningful degree, possibly due to increasing intercenter variability in symptom scoring during the study However, this treatment was associated with a favorable effect on neuropathic deficits without causing significant adverse reactions Long-term trials that focus on neuropathic deficits rather than symptoms as the primary criterion of efficacy are needed to see whether oral treatment with alpha-lipoic acid over several years may slow or reverse the progression of diabetic neuropathy
TL;DR: This work shows that mice with a disrupted gene coding for poly (ADP-ribose) polymerase (PARP–/– mice) are completely resistant to the development of diabetes induced by the beta-cell toxin streptozocin, identifying NAD+ depletion caused by PARP activation as the dominant metabolic event in islet-cell destruction.
Abstract: Human type 1 diabetes results from the selective destruction of insulin-producing pancreatic beta cells during islet inflammation. Cytokines and reactive radicals released during this process contribute to beta-cell death. Here we show that mice with a disrupted gene coding for poly (ADP-ribose) polymerase (PARP–/– mice) are completely resistant to the development of diabetes induced by the beta-cell toxin streptozocin. The mice remained normoglycemic and maintained normal levels of total pancreatic insulin content and normal islet ultrastructure. Cultivated PARP–/– islet cells resisted streptozocin-induced lysis and maintained intracellular NAD+ levels. Our results identify NAD+ depletion caused by PARP activation as the dominant metabolic event in islet-cell destruction, and provide information for the development of strategies to prevent the progression or manifestation of the disease in individuals at risk of developing type 1 diabetes.
Journal Article•
TL;DR: A complex regulatory balance between the different isoforms of survivin might determine the response to proapoptotic stimuli, not only in human RCCs but also in fetal tissues and other types of cancer.
Abstract: Recently, a novel antiapoptosis gene, i.e., survivin, was identified as a structurally unique member of the inhibitor of apoptosis protein family. Survivin expression is turned off during fetal development and not found in non-neoplastic adult human tissues but is again turned on in the most common human cancers. The antiapoptotic properties of survivin might provide a significant growth advantage in tumors and possibly also contribute to chemoresistance of cancer. Therefore, we analyzed the expression of survivin in human renal cell carcinomas (RCCs), known to be largely resistant to chemotherapy. Northern blot analysis and RT-PCR revealed survivin expression in newly established RCC cell lines (n = 11) of all major histological types. Moreover, we identified two novel splice variants of survivin, lacking exon 3 (survivin-ΔEx3) or retaining a part of intron 2 as a cryptic exon (survivin-2B). Both sequence alterations cause marked changes in the structure of the corresponding proteins, including structural modifications of the baculovirus inhibitor of apoptosis protein repeat domain. The role of the novel isoforms in the regulation of apoptosis was assessed in transfection experiments, showing conservation of antiapoptotic properties for survivin-ΔEx3 and a markedly reduced antiapoptotic potential for survivin-2B. In conclusion, our observations suggest a complex regulatory balance between the different isoforms of survivin, which might determine the response to proapoptotic stimuli, not only in human RCCs but also in fetal tissues and other types of cancer.
TL;DR: In this paper, the authors investigated the effects of patients' self-management of oral anticoagulation therapy on accuracy of control and measures of treatment-related quality of life in a randomized, single-blind, multicenter trial.
Abstract: ContextControl of oral anticoagulation therapy has been
reported to often be inadequate. Previous retrospective investigations
suggest that patients' self-adjustment of oral anticoagulants may lead
to improved control.ObjectiveTo investigate the effects of patients' self-management
of oral anticoagulation therapy on accuracy of control and measures of
treatment-related quality of life.DesignRandomized, single-blind, multicenter trial.Setting and ParticipantsA total of 179 patients receiving
long-term oral anticoagulation treatment were enrolled at 5 referral
centers in Germany.InterventionPatients were randomized to an oral anticoagulation
self-management group based on a structured treatment and teaching
program and international normalized ratio (INR) self-monitoring. The
control group received conventional care as provided by family
physicians, including referral to specialists if necessary.Main Outcome MeasuresDeviation of INR values from the individual
INR target range (squared) and the 5 categories of treatment-related
quality of life.ResultsDeviation of INR value from the mean of the INR
target range was significantly lower in the intervention group at
3-month (squared INR deviation, 0.59 vs 0.95; P<.001) and
6-month follow-up (0.65 vs 0.83; P=.03)
compared with the control group. Also, the intervention group had INR
values within the target range more often (repeated measurement
analysis for categorical data, P=.006). The
results were mainly due to less frequent suboptimal INR values in the
intervention group (32.8% vs 50.0% [P=.03]
at 3-month, and 33.7% vs 48.2% [P=.08] at
6-month follow-up). Treatment-related quality-of-life measures,
especially treatment satisfaction scores, were significantly higher in
the intervention group compared with controls.ConclusionsAn anticoagulation education program that
includes self-management of anticoagulation therapy results in improved
accuracy of anticoagulation control and in treatment-related
quality-of-life measures. Further studies are needed to describe
whether the program will reduce risk of bleeding or
thromboembolism.
TL;DR: The endosymbiont hypothesis for the origins of plastids (and mitochondria, which will not be further discussed here) was very popular among biologists and fell into disfavour shortly after the First World War and remained scorned for 50 years.
Abstract: That plastids were once free-living cyanobacteria is now taken for granted by many, and for good reasons, for there is a wealth of data – in particular from the comparison of plastid and cyanobacterial genomes – that support this view. There is currently no seriously entertained alternative hypothesis to the view that plastids descend from cyanobacteria. But that was not always the case. Well into the 1970s there was a generally favoured alternative hypothesis, namely that early in evolution plastids arose de novo from within a non-plastid bearing cell (an autogenous origin) rather than through invasion by a cyanobacterium into a non-plastid-bearing cell with subsequent intracellular coexistence and reduction to an organelle (an endosymbiotic origin). Interestingly, the shift from autogenous to endosymbiotic hypotheses during the 1970s was a reversal of state for during the first two decades of this century, the endosymbiont hypothesis for the origins of plastids (and mitochondria, which will not be further discussed here) was very popular among biologists. It fell into disfavour shortly after the First World War, for reasons that are very difficult to summarize briefly, and remained scorned for 50 years (see Sapp, 1994, for an historical account in English, and Hoxtermann, 1998, for a succinct historical account in German). So where did the first version of the endosymbiont hypothesis come from? In a nutshell, it came from Konstantin Sergejewiz Merezkovskij (usually written as Constantin Mereschkowsky), a Russian botanist of little standing who worked at a rather small and by no means prominent university in Kasan and who published a very remarkable paper in 1905. We are not aware of any true precedent for his paper, which draws upon three lines of evidence known at the time.
TL;DR: Improved data acquisition and processing strategies for blood oxygenation level‐dependent (BOLD)‐contrast functional magnetic resonance imaging (fMRI), which enhance the functional contrast‐to‐noise ratio (CNR) by sampling multiple echo times in a single shot, are described.
Abstract: Improved data acquisition and processing strategies for blood oxygenation level-dependent (BOLD)-contrast functional magnetic resonance imaging (fMRI), which enhance the functional contrast-to-noise ratio (CNR) by sampling multiple echo times in a single shot, are described. The dependence of the CNR on T2*, the image encoding time, and the number of sampled echo times are investigated for exponential fitting, echo summation, weighted echo summation, and averaging of correlation maps obtained at different echo times. The method is validated in vivo using visual stimulation and turbo proton echoplanar spectroscopic imaging (turbo-PEPSI), a new single-shot multi-slice MR spectroscopic imaging technique, which acquires up to 12 consecutive echoplanar images with echo times ranging from 12 to 213 msec. Quantitative T2*-mapping significantly increases the measured extent of activation and the mean correlation coefficient compared with conventional echoplanar imaging. The sensitivity gain with echo summation, which is computationally efficient provides similar sensitivity as fitting. For all data processing methods sensitivity is optimum when echo times up to 3.2 T2* are sampled. This methodology has implications for comparing functional sensitivity at different magnetic field strengths and between brain regions with different magnetic field inhomogeneities.
TL;DR: The picture that has emerged connects this pathway to a variety of other cellular processes, such as cell cycle progression, mating, nutrients sensing, nutrient sensing, calcium homeostasis and the structural dynamics of the cytoskeleton.
Abstract: Signal transduction mediated by the single yeast isozyme of protein kinase C (Pkc1p) is essential for the maintenance of cellular integrity in this model eukaryote. The past few years have seen a dramatic increase in our knowledge of the upstream regulatory factors that modulate Pkc1p activity (e.g. Tor2p, Rom1p, Rom2p, Rho1p, Slg1p, Mid2p) and of the downstream targets of the MAP kinase cascade triggered by it (e.g. Rlm1p, SBF complex). The picture that has emerged connects this pathway to a variety of other cellular processes, such as cell cycle progression (Cdc28p, Swi4p), mating (Ste20p), nutrient sensing (Ira1p), calcium homeostasis (calcineurin, Mid2p, Fks2p) and the structural dynamics of the cytoskeleton (Spa1p, Bni1p).
TL;DR: Evidence is provided for the involvement of reactive oxygen species in the generation of aging-associated mtDNA lesions in human cells and indicate a previously unrecognized role of singlet oxygen in photoaging of human skin.
TL;DR: The versatility of integrons is described, especially their mobility and their ability to collect resistance genes, which are an important source for the spread of antibiotic resistance.
Abstract: Integrons are genetic elements that, although unable to move themselves, contain gene cassettes that can be mobilized to other integrons or to secondary sites in the bacterial genome. The majority of approximately 60 known gene cassettes encode resistance to antibiotics. Recently, a number of gene cassettes encoding extended-spectrum beta-lactamases or carbapenemases have been described. Up to at least five cassettes may be present in an integron, which leads to multiresistance. Frequently, more than one integron is observed within the same bacterial cell. Integrons are widespread in their species distribution. Although integrons are normally reported from Enterobacteriaceae and other gram-negative bacteria, an integron has been described in Corynebacterium glutamicum, a gram-positive species. The gene cassette in this integron showed even higher expression when compared to the expression in Escherichia coli. Integrons have been reported from all continents and are found frequently. The widespread occurrence of integrons is thought to be due to their association with transposon plasmids, conjugative plasmids, or both. Integrons form an important source for the spread of antibiotic resistance, at least in gram-negative bacteria but also potentially in gram-positive bacteria. The aim of this review is to describe the versatility of integrons, especially their mobility and their ability to collect resistance genes.
TL;DR: Anatomical atlases based on this procedure provide a new tool for the interpretation of structural data obtained from functional imaging techniques, and offers a new level of reproducibility and observer independence.
TL;DR: The epidemiology of each functional anorectal disorders is defined and discussed, their pathophysiology is summarized and diagnostic approaches and treatment are suggested.
Abstract: In this report the functional anorectal disorders, the etiology of which is currently unknown or related to the abnormal functioning of normally innervated and structurally intact muscles, are discussed. These disorders include functional fecal incontinence, functional anorectal pain, including levator ani syndrome and proctalgia fugax, and pelvic floor dyssynergia. The epidemiology of each disorder is defined and discussed, their pathophysiology is summarized and diagnostic approaches and treatment are suggested. Some suggestions for the direction of future research on these disorders are also given.
TL;DR: In this article, a PET study using 15O-butanol was conducted to examine the neural correlates of reading and of the phonological conversion of legal letter strings, with or without meaning.
Abstract: Silent reading and reading aloud of German words and pseudowords were used in a PET study using (15O)butanol to examine the neural correlates of reading and of the phonological conversion of legal letter strings, with or without meaning. The results of 11 healthy, right-handed volunteers in the age range of 25 to 30 years showed activation of the lingual gyri during silent reading in comparison with viewing a fixation cross. Comparisons between the reading of words and pseudowords suggest the involvement of the middle temporal gyri in retrieving both the phonological and semantic code for words. The reading of pseudowords activates the left inferior frontal gyrus, including the ventral part of Broca's area, to a larger extent than the reading of words. This suggests that this area might be involved in the sublexical conversion of orthographic input strings into phonological output codes. (Pre)motor areas were found to be activated during both silent reading and reading aloud. On the basis of the obtained activation patterns, it is hypothesized that the articulation of high-frequency syllables requires the retrieval of their concomitant articulatory gestures from the SMA and that the articulation of low-frequency syllables recruits the left medial premotor cortex.