Showing papers by "University of Göttingen published in 1996"
TL;DR: This biennial Review summarizes much of particle physics, using data from previous editions.
12,798 citations
TL;DR: Ten cases of Creutzfeldt-Jakob disease have been identified in the UK in recent months with a new neuropathological profile that raises the possibility that they are causally linked to BSE.
2,574 citations
TL;DR: The presence of not one but three spermatogenesis loci in Yq11 is proposed and that each locus is active during a different phase of male germ cell development.
Abstract: In a large collaborative screening project, 370 men with idiopathic azoospermia or severe oligozoospermia wereanalysed for deletions of 76 DNA loci in Yq11. In 12 individuals, we observed de novo microdeletions involvingseveral DNA loci, while an additional patient had an inherited deletion. They were mapped to three differentsubregions in Yq11. One subregion coincides to the AZF region defined recently in distal Yq11. The second andthird subregion were mapped proximal to it, in proximal and middle Yq11, respectively. The different deletionsobserved were not overlapping but the extension of the deleted Y DNA in each subregion was similar in eachpatient analysed. In testis tissue sections, disruption of spermatogenesis was shown to be at the same phasewhen the microdeletion occurred in the same Yq11 subregion but at a different phase when the microdeletionoccurred in a different Yq11 subregion. Therefore, we propose the presence of not one but three spermatogenesisloci in Yq11 and that each locus is active during a different phase of male germ cell development. As the mostsevere phenotype after deletion of each locus is azoospermia, we designated them as: AZFa, AZFb and AZFc.Their probable phase of function in human spermatogenesis and candidate genes involved will be discussed. INTRODUCTIONGenes for male germ cell development are present on the Ychromosome in different species groups (1–3). In men, theposition of a spermatogenesis locus was mapped in theeuchromatic part of the long Y arm (Yq11). It was called‘azoospermia factor’ (AZF), as the first six men observed withterminal deletions in Yq were azoospermic (4). Mature spermcells were not detectable in their seminal fluid. In all cases, the Ydeletions included the large heterochromatin block of the long Yarm (Yq12) and an undefined amount of the adjacent euchromatin(Yq11). Subsequently, the presence of AZF in Yq11 wasconfirmed by numerous studies at both cytogenetic (5) andmolecular level (6–8). However, the genetic complexity of AZFcould not be revealed by these analyses.This first became possible by the detection of sterile patientswith small interstitial deletions (i.e. microdeletions) in Yq11. Ina study with 13 sterile men suffering from idiopathic azoospermiatwo different microdeletions in Yq11 were observed (9). Theywere mapped to two non overlapping positions in Yq11 interval6 (10). However, further studies of Yq11 microdeletionsassociated to the phenotype of male sterility, only confirmed theposition of an AZF locus in distal Yq11 (11,12). The mostextensive study was performed by Reijo et al. (13) on 89 sterile
1,246 citations
TL;DR: It is concluded that the changes in intracortical excitability are caused by GABA‐controlled interneuronal circuits in the motor cortex while changes in motor threshold are dependent on ion channel conductivity and may reflect membrane excitability.
Abstract: The effect of a single oral dose of various antiepileptic drugs on the excitability of the motor system was studied in healthy volunteers by means of transcranial magnetic stimulation. Motor threshold, duration of the cortical silent period, and intracortical excitability after double-shock transcranial stimulation were tested before and at defined intervals after drug intake. Antiepileptic drugs that support the action of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the neocortex (vigabatrin, baclofen) reduced intracortical excitability but had no effect on motor threshold. Gabapentin, whose mechanism of action has not yet been unequivocally identified, showed a similar profile. By contrast, sodium and calcium channel blockers without considerable neurotransmitter properties (carbamazepine, lamotrigine, losigamone) elevated motor threshold but did not change intracortical excitability. The cortical silent period was lengthened by gabapentin and carbamazepine. Changes in peripheral motor excitability (maximum M wave, peripheral silent period) were not observed. We conclude that the changes in intracortical excitability are caused by GABA-controlled interneuronal circuits in the motor cortex while changes in motor threshold are dependent on ion channel conductivity and may reflect membrane excitability. Transcranial magnetic stimulation may be a promising noninvasive approach to study the selective effects of antiepileptic drugs on brain function.
1,085 citations
TL;DR: The effectiveness and validity of 11 important mood induction procedures (MIPs) were comparatively evaluated by meta-analytical procedures as discussed by the authors, and two hundred and fifty effects of the experimental induction of positive, elated and negative, depressed mood in adult, non-clinical samples were integrated.
Abstract: The effectiveness and validity of 11 important mood induction procedures (MIPs) were comparatively evaluated by meta-analytical procedures. Two hundred and fifty effects of the experimental induction of positive, elated and negative, depressed mood in adult, non-clinical samples were integrated. Effect sizes were generally larger for negative than for positive mood inductions. The presentation of a film or story turned out to be most effective in inducing both positive and negative mood states. The effects are especially large when subjects are explicitly instructed to enter the specified mood state. For elated mood, all other MIPs yielded considerably lower effectiveness scores. For the induction of negative mood states, Imagination, Velten, Music, Social Interaction and Feedback MIPs were about as effective as the Film/Story MIP without instruction. Induction effects covaried with several study characteristics. Effects tend to be smaller when demand characteristics are controlled or subjects are not informed about the purpose of the experiment. For behavioural measures, effects are smaller than for self-reports but still larger than zero. Hence, the effects of MIPs can be partly, but not fully due to demand effects.
1,059 citations
TL;DR: Necessary and sufficient conditions for the occurrence of generalized synchronization of unidirectionally coupled dynamical systems are given in terms of asymptotic stability and the existence of generalized synchronized systems in the case of parameter mismatch between coupled systems leads to a new interpretation of recent experimental results.
Abstract: Necessary and sufficient conditions for the occurrence of generalized synchronization of unidirectionally coupled dynamical systems are given in terms of asymptotic stability The relation between generalized synchronization, predictability, and equivalence of dynamical systems is discussed All theoretical results are illustrated by analytical and numerical examples In particular, the existence of generalized synchronization in the case of parameter mismatch between coupled systems leads to a new interpretation of recent experimental results Furthermore, the possible application of generalized synchronization for attractor reconstruction in nonlinear time series analysis is discussed
880 citations
TL;DR: The effect of the short-acting benzodiazepine lorazepam on motor cortex excitability was investigated in 11 healthy volunteers using the technique of focal transcranial magnetic stimulation to assess various aspects of motor system excitability and the relevance of the present data in clinical epileptology is discussed.
Abstract: The effect of the short-acting benzodiazepine lorazepam on motor cortex excitability was investigated in 11 healthy volunteers using the technique of focal transcranial magnetic stimulation. The threshold intensity for evoking an electromyographic response in the resting and active abductor digiti minimi muscle, the size of the motor evoked potential, the duration of the cortical and peripheral silent periods, the corticocortical inhibition and facilitation after paired magnetic stimuli, and the transcallosal inhibition were used as parameters to assess various aspects of motor system excitability. Baseline values were compared with data obtained 2, 5 and 24 h after a single oral dose of 2.5 mg lorazepam. Resting and active motor thresholds and the size of the motor evoked potential remained unchanged. The duration of the cortical silent period was prolonged with a maximum effect 5 h after drug intake, while the peripheral silent period did not show any lengthening at that time. The corticocortical inhibition showed a tendency toward more inhibition, while the corticocortical facilitation was almost completely suppressed. The transcallosal inhibition showed an inconsistent trend to less inhibition. In parallel to the pharmacokinetics of lorazepam, all effects peaked at 2 h and 5 h, and were (partially) reversible after 24 h. It is hypothesized that most of these findings are due to the reinforcement of GABA action by lorazepam at the level of the motor cortex. The lack of effect on motor threshold and on the size of the motor evoked potential may indicate that these parameters are physiologically distinct from corticocortical excitability and the cortical silent period. The relevance of the present data in clinical epileptology is discussed.
747 citations
TL;DR: Heterogenous liver tissue is the result of zonal differences in the activation of the cellular genome caused by gradients in oxygen, substrate, hormone, and mediator levels, in innervation, as well as in cell-to-cell and cell- to-biomatrix interactions.
Abstract: The enormous number of different liver functions are carried out by parenchymal and four main types of nonparenchymal cells, either alone or in cooperation. Although the liver tissue is uniform on the level of histology, it is heterogenous on the level of morphometry and histochemistry. This heterogeneity is related to the blood supply; cells located in the upstream or periportal zone differ from those in the downstream or perivenous zone in their equipment with key enzymes, translocators, receptors, and subcellular structures and therefore have different functional capacities. This is the basis of the model of metabolic zonation, according to which glucose release from glycogen and via gluconeogenesis, amino acid utilization and ammonia detoxification, protective metabolism, bile formation, and the synthesis of certain plasma proteins such as albumin and fibrinogen occur mainly in the periportal area, whereas glucose utilization, xenobiotic metabolism, and the formation of other plasma proteins such as alpha 1-antitrypsin or alpha-fetoprotein occur predominantly in the perivenous zone. The mor- phologic and functional heterogeneity is the result of zonal differences in the activation of the cellular genome caused by gradients in oxygen, substrate, hormone, and mediator levels, in innervation, as well as in cell-to-cell and cell-to-biomatrix interactions.
513 citations
TL;DR: The combined direct and microglia-mediated effects of PrP106–126 are toxic to normal neurons but are insufficient to destroy neurons from mice not expressing PrPc.
Abstract: THE prion protein PrPc is a glycoprotein of unknown function1 normally found in neurons2 and glia3. It is involved in diseases such as bovine spongiform encephalopathy (BSE), scrapie and Creutzfeldt–Jakob disease4. PrPSc, an altered isoform of PrPc that is associated with disease, shows greater protease resistance and is part of the infectious agent, the prion5,6. Prion diseases are characterized by neuronal degeneration, gliosis and accumulation of PrPSc (ref. 7). Mice devoid of PrPc are resistant to scrapie8. A fragment of human PrP consisting of amino acids 106–126 that forms fibrils in vitro is toxic to cultured neurons9–11. Here we show that this toxic effect requires the presence of microglia which respond to PrP106–126 by increasing their oxygen radical production. The combined direct and microglia-mediated effects of PrP106–126 are toxic to normal neurons but are insufficient to destroy neurons from mice not expressing PrPc.
513 citations
496 citations
TL;DR: Fludarabine provided an effective and well-tolerated therapy for patients with advanced CLL, which compared favourably with CAP as one of the most effective standard regimens.
TL;DR: Exogenous GLP-1 is able to lower fasting glycemia also in type I diabetic patients, mainly by reducing glucagon concentrations, however, this alone is not sufficient to normalize fasting plasma glucose concentrations, as was previously observed in type II diabetic patients.
Abstract: OBJECTIVE Glucagon-like peptide I(7–36) amide (GLP-1) is a physiological incretin hormone that, in slightly supraphysiological doses, stimulates insulin secretion, lowers glucagon concentrations, and thereby normalizes elevated fasting plasma glucose concentrations in type II diabetic patients. It is not known whether GLP-1 has effects also in fasting type I diabetic patients. RESEARCH DESIGN AND METHODS In 11 type I diabetic patients (HbA 1c 9.1 ± 2.1%; normal, 4.2–6.3%), fasting hyperglycemia was provoked by halving their usual evening NPH insulin dose. In random order on two occasions, 1.2 pmol · kg −1 · min −1 GLP-1 or placebo was infused intravenously in the morning (plasma glucose 13.7 ± 0.9 mmol/l; plasma insulin 26 ± 4 pmol/l). Glucose (glucose oxidase method), insulin, C-peptide, glucagon, GLP-1, cortisol, growth hormone (immunoassays), triglycerides, cholesterol, and nonesterified fatty acids (enzymatic tests) were measured. RESULTS Glucagon was reduced from ∼8 to 4 pmol/l, and plasma glucose was lowered from 13.4 ± 1.0 to 10.0 ± 1.2 mmol/l with GLP-1 administration (plasma concentrations ∼100 pmol, P P P = 0.34), triglycerides ( P = 0.57), cholesterol ( P = 0.64), cortisol ( P = 0.40), or growth hormone ( P = 0.53). CONCLUSIONS Therefore, exogenous GLP-1 is able to lower fasting glycemia also in type I diabetic patients, mainly by reducing glucagon concentrations. However, this alone is not sufficient to normalize fasting plasma glucose concentrations, as was previously observed in type II diabetic patients, in whom insulin secretion (C-peptide response) was stimulated 20-fold.
TL;DR: An overview on the biodegradation of PHA is given to give an overview of the metabolism and biotechnological aspects of P HA and PHA depolymerases.
Abstract: Stimulated by the commercial availability of bacteriologically produced polyesters such as poly[(R)-3-hydroxybutyric acid], and encouraged by the discovery of new constituents of polyhydroxyalkanoic acids (PHA), a considerable body of knowledge on the metabolism of PHA in microorganisms has accumulated. The objective of this essay is to give an overview on the biodegradation of PHA. The following topics are discussed: (i) general considerations of PHA degradation, (ii) methods for identification and isolation of PHA-degrading microorganisms, (iii) characterization of PHA-degrading microorganisms, (iv) biochemical properties of PHA depolymerases, (v) mechanisms of PHA hydrolysis, (vi) regulation of PHA depolymerase synthesis, (vii) molecular biology of PHA depolymerases, (viii) influence of the physicochemical properties of PHA on its biodegradability, (ix) degradation of polyesters related to PHA, (x) biotechnological aspects of PHA and PHA depolymerases.
TL;DR: In this paper, a two-dimensional numerical convection model was used to study the influence of trench migration on the ability of subducted slabs to penetrate an endothermic phase boundary at 660 km depth.
TL;DR: Ergosterol and microbial biomass C were measured in 26 arable, 16 grassland and 30 forest soils as discussed by the authors, where the ergosterol content ranged from 0.75 to 12.94 μg g-1 soil.
Abstract: Ergosterol and microbial biomass C were measured in 26 arable, 16 grassland and 30 forest soils. The ergosterol content ranged from 0.75 to 12.94 μg g-1 soil. The geometric mean ergosterol content of grassland and forest soils was around 5.5 μg g-1, that of the arable soils 2.14 μg g-1. The ergosterol was significantly correlated with biomass C in the entire group of soils, but not in the subgroups of grassland and forest soils. The geometric mean of the ergosterol: microbial biomass C ratio was 6.0 mg g-1, increasing in the order grassland (5.1), arable land (5.4) and woodland (7.2). The ergosterol:microbial biomass C ratio had a strong negative relationship with the decreasing cation exchange capacity and soil pH, indicating that the fungal part of the total microbial biomass in soils increased when the buffer capacity decreased. The average ergosterol concentration calculated from literature data was 5.1 mg g-1 fungal dry weight. Assuming that fungi contain 46% C, the conversion factor from micrograms ergosterol to micrograms fungal biomass C is 90. For soil samples, neither saponification of the extract nor the more effective direct saponification during extraction seems to be really necessary.
TL;DR: Intravenous glucagon-like peptide (GLP-1) can normalize plasma glucose in non-insulin-dependent diabetic (NIDDM) patients and has similar effects in NIDDM patients as an intravenous infusion, in the short term.
Abstract: Intravenous glucagon-like peptide (GLP)-1 [7–36 amide] can normalize plasma glucose in non-insulin-dependent diabetic (NIDDM) patients. Since this is no form for routine therapeutic administration, effects of subcutaneous GLP-1 at a high dose (1.5 nmol/kg body weight) were examined. Three groups of 8, 9 and 7 patients (61 ± 7, 61 ± 9, 50 ± 11 years; BMI 29.5 ± 2.5, 26.1 ± 2.3, 28.0 ± 4.2 kg/m2; HbA1 c 11.3 ± 1.5, 9.9 ± 1.0, 10.6 ± 0.7 %) were examined: after a single subcutaneous injection of 1.5 nmol/kg GLP [7–36 amide]; after repeated subcutaneous injections (0 and 120 min) in fasting patients; after a single, subcutaneous injection 30 min before a liquid test meal (amino acids 8 %, and sucrose 50 g in 400 ml), all compared with a placebo. Glucose (glucose oxidase), insulin, C-peptide, GLP-1 and glucagon (specific immunoassays) were measured. Gastric emptying was assessed with the indicator-dilution method and phenol red. Repeated measures ANOVA was used for statistical analysis. GLP-1 injection led to a short-lived increment in GLP-1 concentrations (peak at 30–60 min, then return to basal levels after 90–120 min). Each GLP-1 injection stimulated insulin (insulin, C-peptide, p < 0.0001, respectively) and inhibited glucagon secretion (p < 0.0001). In fasting patients the repeated administration of GLP-1 normalized plasma glucose (5.8 ± 0.4 mmol/l after 240 min vs 8.2 ± 0.7 mmol/l after a single dose, p = 0.0065). With the meal, subcutaneous GLP-1 led to a complete cessation of gastric emptying for 30–45 min (p < 0.0001 statistically different from placebo) followed by emptying at a normal rate. As a consequence, integrated incremental glucose responses were reduced by 40 % (p = 0.051). In conclusion, subcutaneous GLP-1 [7–36 amide] has similar effects in NIDDM patients as an intravenous infusion. Preparations with retarded release of GLP-1 would appear more suitable for therapeutic purposes because elevation of GLP-1 concentrations for 4 rather than 2 h (repeated doses) normalized fasting plasma glucose better. In the short term, there appears to be no tachyphylaxis, since insulin stimulation and glucagon suppression were similar upon repeated administrations of GLP-1 [7–36 amide]. It may be easier to influence fasting hyperglycaemia by GLP-1 than to reduce meal-related increments in glycaemia. [Diabetologia (1996) 39: 1546–1553]
TL;DR: Assessment of current knowledge on the myelomonocytic origin and successive differentiation of human T-cell-directed DCs suggests that these cells may even differentiate from blood monocytes.
TL;DR: Monitoring patient survival, a practice routinely employed by many cancer registries, is an essential component of the evaluation of progress against cancer.
Abstract: BACKGROUND
Monitoring patient survival, a practice routinely employed by many cancer registries, is an essential component of the evaluation of progress against cancer. However, changes in prognosis over time are disclosed with considerable delay, with traditional methods of monitoring cumulative survival.
METHODS
This article introduces an alternative approach, denoted “period monitoring,” which aims at more timely detection of such changes. The conceptual background and the computational realization of the proposed method are outlined, and its application is illustrated by an empirical example from the population-based cancer registry of Saarland, Germany.
RESULTS
The principle of period monitoring is shown to be analogous to the well-established use of period life tables in the field of demography. Computational realization of period monitoring can be achieved with simple modifications of standard survival analysis techniques. Compared with traditional methods of monitoring survival, period monitoring can advance detection of changes in cumulative survival considerably.
CONCLUSIONS
Despite some limitations with respect to the ease of data interpretation, period monitoring offers a useful supplement to existing methods of monitoring patient survival. Cancer 1996;78:2004-10.
TL;DR: The presence of HPV DNA in a large percentage of specimens of nonmelanoma carcinomas of the skin from immunosuppressed patients, as well as from nonimmmunosuppression patients, renders a papillomavirus infection as a possible factor in the etiology of this disease.
Abstract: Background : Nonmelanoma carcinomas of the skin represent the most frequent cancers among the Caucasian population worldwide. They occur with high frequency in renal allograft recipient patients after prolonged immunosuppression. Purpose : We analyzed tumors obtained from both immunosuppressed and nonimmunosuppressed patients for human papillomavirus (HPV) DNA. Methods : Twenty-nine specimens of nonmelanoma carcinomas of the skin were obtained from 19 renal allograft recipient patients ; these included 20 specimens of squamous cell carcinoma (SCC) from 11 patients, five specimens of basal cell carcinoma (BCC) from four patients, and four specimens of carcinoma in situ (CIS) from four patients. Forty-one specimens of nonmelanoma carcinomas of the skin were obtained from 32 nonimmunosuppressed patients ; these included 26 SCC specimens from 19 patients, 11 BCC specimens from nine patients, and four keratoacanthoma (benign epithelial tumor) specimens from four patients. A polymerase chain reaction method involving use of degenerate oligonucleotide primers, in which the conserved region of the open reading frame of the HPV L1 (major capsid protein) gene is amplified, was used to amplify total cellular DNA purified from individual tumors. The DNA of each specimen was subjected to 16 different amplification reactions ; different primer combinations were used in order to increase the sensitivity and specificity of HPV detection. Resulting products were probed with a radioactively labeled, degenerate oligonucleotide. HPV-specific DNA was either sequenced directly after elution from the gel or amplified with semi-nested, degenerate primers, after which the products were cloned and sequenced. Sequences were compared with all known papillomavirus sequences. Results : Thirteen (65%) of the 20 SCC specimens and three of the five BCC specimens from immunosuppressed (renal allograft recipient) patients contained identifiable HPV-related sequences, among them 13 putative novel HPV genomes. In addition, all other malignant tumor specimens from this patient group revealed faint signals upon amplification and hybridization ; the origin of these signals has not been identified in the present study. In nonimmunosuppressed patients, eight (31%) of 26 SCC specimens and four (36%) of 11 BCC specimens contained sequences of HPV types. Two putative novel HPV sequences could be identified in this group. Faint signals of yet undetermined origin were observed in eight of the SCC specimens and in two of the BCC specimens. Two of four keratoacanthoma specimens contained sequences of known HPV type. (Keratoacanthoma is a nonmalignant lesion for which the natural history has not been defined.) The spectrum of HPV types in both groups of patients differed substantially. Conclusions : These data point to the frequent presence of HPV sequences in SCCs and BCCs of the skin. The etiologic relationship of these infections to the respective malignant tumors remains to be evaluated. Implications : The presence of HPV DNA in a large percentage of specimens of nonmelanoma carcinomas of the skin from immunosuppressed patients, as well as from nonimmunosuppressed patients, renders a papillomavirus infection as a possible factor in the etiology of this disease
TL;DR: Strain PD630 utilized β-oxidation and de novo fatty acid biosynthesis for the synthesis of storage lipids and lipid inclusions seemed to have definite structures, probably with membranes at their surfaces, which allow them to maintain their shape, and with some associated proteins, probably involved in the inclusion formation.
Abstract: An oleaginous hydrocarbon-degrading Rhodococcus opacus strain (PD630) was isolated from a soil sample. The cells were able to grow on a variety of substrates and to produce large amounts of three different types of intracellular inclusions during growth on alkanes, phenylalkanes, or non-hydrocarbon substrates. Electron microscopy revealed large numbers of electron-transparent inclusions with a sphere-like structure. In addition, electron-dense inclusions representing polyphosphate and electron-transparent inclusions with an elongated disc-shaped morphology occurred in small amounts. The electron-transparent inclusions of alkane- or gluconate-grown cells were composed of neutral lipids (98%, w/w), phospholipids (1.2%, w/w), and protein (0.8%, w/w). The major component of the cellular inclusions was triacylglycerols; minor amounts of diacylglycerols and probably also some free fatty acids were also present. Free fatty acids and/or fatty acids in acylglycerols in cells of R. opacus amounted up to 76 or 87% of the cellular dry weight in gluconate- or olive-oil-grown cells, respectively. The fatty acid composition of the inclusions depended on the substrate used for cultivation. In cells cultivated on n-alkanes, the composition of the fatty acids was related to the substrate, and intermediates of the β-oxidation pathway, such as hexadecanoic or pentadecanoic acid, were among the acylglycerols. Hexadecanoic acid was also the major fatty acid (up 36% of total fatty acids) occurring in the lipid inclusions of gluconate-grown cells. This indicated that strain PD630 utilized β-oxidation and de novo fatty acid biosynthesis for the synthesis of storage lipids. Inclusions isolated from phenyldecane-grown cells contained mainly the non-modified substrate and phenylalkanoic acids derived from the hydrocarbon oxidation, such as phenyldecanoic acid, phenyloctanoic acid, and phenylhexanoic acid, and approximately 5% (w/w) of diacylglycerols. The lipid inclusions seemed to have definite structures, probably with membranes at their surfaces, which allow them to maintain their shape, and with some associated proteins, probably involved in the inclusion formation.
TL;DR: The copurification of calreticulin and endomannosidase from a Golgi fraction in comparable amounts and the strikingly similar saccharide specificities of the chaperone and the processing enzyme have suggested a tentative model for the dissociation through glucose removal of calReticulin-glycoprotein complexes in a post-endoplasmic reticulum locale.
TL;DR: Immunohistochemistry with antibodies against the prion protein combined with special tissue pretreatment regimens gives reliable diagnostic results and is superior to other techniques that may be more sensitive but require fresh, unfixed brain tissue.
Abstract: Background: Making a clinical diagnosis of sporadic Creutzfeldt-Jakob disease relies on the evaluation of rapidly progressive dementia, ataxia, myoclonus, changes on the electroencephalogram, and other neurological signs. A definite diagnosis, however, is confined to cases that have been evaluated neuropathologically or by equivalent diagnostic techniques. This places a high priority on the establishment of reliable neuropathologic methods for the investigation and diagnosis of Creutzfeldt-Jakob disease. Objective: To evaluate existing morphological and laboratory diagnostic techniques to reach a consensus on the definition of "definite Creutzfeldt-Jakob disease." Methods: The existing morphological techniques, particularly immunohistochemistry, used in 4 laboratories—Germany, Great Britain, Japan, and the United States—are evaluated, and various laboratory diagnostic techniques are discussed. Results: Immunohistochemistry with antibodies against the prion protein combined with special tissue pretreatment regimens gives reliable diagnostic results and, for its applicability to formalin-fixed and paraffin-embedded tissue, is superior to other techniques that may be more sensitive but require fresh, unfixed brain tissue. Conclusions: Our experience suggests the following regimen for the diagnosis of suspected Creutzfeldt-Jakob disease: light microscopy of various brain regions, which in typical cases may lead to definite diagnosis. Immunohistochemistry with antibodies against the prion protein is preferable in all suspected cases of Creutzfeldt-Jakob disease and is mandatory whenever a routine histological workup does not yield definite results. Additional special techniques can be applied if required.
TL;DR: A special feature of synchronizing systems where a system with slowly varying parameters converges from a state of nonsynchroniza to synchronization is discussed, governed by additional ordinary differential equations for parameters that are controlled by the synchronization.
Abstract: s The synchronization of (unidirectionally) coupled dy namical systems and its possible applications in commu cation schemes is currently a field of great interest ( [1–7] and references cited therein). In this Letter w discuss a special feature of synchronizing systems ca autosynchronizationwhere a system with slowly varying parameters converges from a state of nonsynchroniza to synchronization. This adaption process is governed additional ordinary differential equations (ODEs) for th parameters that are controlled by the synchronization er A systematic way for deriving the parameter controllin loop is presented and illustrated by numerical examp For the sake of brevity we consider unidirectionally co pled systems only, although the main ideas can in princ also be applied to mutually coupled synchronizing syste In order to indicate a possible application in nonlinear tim series analysis [8] and system identification autosynch nization is discussed and used in the following for es mating the parameters of a given model from a scalar ti series [9–14]. Let
TL;DR: Examining dimerisation of the glycophorin A transmembrane segment in a natural membrane employing the ToxR transcription activator from Vibrio cholerae found it to be less sensitive to mutations when localised within a natural lipid bilayer compared to measurements in detergent solution.
TL;DR: This blinded electroencephalogram study in Creutzfeldt-Jakob disease confirms the high diagnostic value of electroencephalography, as previously reported by open studies.
Abstract: Objective: To assess the sensitivity, specificity, and interobserver reliability of periodic sharp wave complexes in the electroencephalograms of patients with Creutzfeldt-Jakob disease. Design: Sixty-eight electroencephalograms in 29 patients who had been suspected of having Creutzfeldt-Jakob disease were reanalyzed by an investigator who was unaware of the clinical data. The incidence of periodic sharp wave complexes in neuropathologically confirmed Creutzfeldt-Jakob disease vs progressive dementia other than Creutzfeldt-Jakob disease was assessed. Blinded electroencephalogram analysis was performed by a second investigator. The interobserver reliability was assessed by the k value. Setting: University hospital, base of the German National Creutzfeldt-Jakob Disease Surveillance Study. Patients: Fifteen patients with neuropathologically confirmed Creutzfeldt-Jakob disease and 14 patients who had been suspected of having Creutzfeldt-Jakob disease because of rapidly progressive dementia but in whom other dementias were diagnosed by unblinded investigators based on clinical and electroencephalographic criteria. Main Outcome Measure: Sensitivity and specifity of periodic sharp wave complexes assessed by their incidence in Creutzfeldt-Jakob disease vs other dementias. Interobserver reliability of periodic sharp wave complexes was expressed by the k value. Results: For periodic sharp wave complexes, blinded electroencephalographic analysis resulted in a sensitivity and a specificity of 67% and 86%, respectively. Interobserver reliability was excellent (k=0.95). Conclusion: This blinded electroencephalographic study in Creutzfeldt-Jakob disease confirms the high diagnostic value of electroencephalography, as previously reported by open studies.
TL;DR: The principal finding of this study is that mutations of the SCA2 and SCA3 gene cause phenotypes which can be distinguished in vivo by recording of eye movements and morphometric MRI analysis.
Abstract: Sixty-five patients suffering from autosomal dominant cerebellar ataxia-I(ADCA-1) were subjected genotype phenotype correlation analysis using molecular genetic assignment to the spinocerebellar ataxia type 1, 2 or 3 (SCA1, -2 or -3) locus, clinical examination, eye movement recording and morphometric analysis of MRIs. Pyramidal tract signs, pale discs and dysphagia were more frequent in SCA1 compared SCA2 and SCA3 patients. Saccade velocity was reduced in 56% of SCA1 and all SCA2, but only in 30% of SCA3 patients. MRIs of SCA2 patients showed atrophy changes typical of severe olivopontocerebellar atrophy (OPCA). The morphological changes in SCA1 were similar but less pronounced. In contrast, SCA3 patients had only mild cerebellar and brain stem atrophy distinct from typical OPCA. The principal finding of this study is that mutations of the SCA2 and SCA3 gene cause phenotypes which can be distinguished in vivo by recording of eye movements and morphometric MRI analysis. Correlative plotting of saccade velocity and diameter of the middle cerebellar peduncle yields a clear separation of SCA2 and SCA3. Spinocerebellar ataxia type I falls into an intermediate range that overlaps with both SCA2 and SCA3. However, the clinical syndrome observed in SCA1 patients is different from that in SCA2 and SCA3.
TL;DR: In this paper, a laser ablation microprobe (LAM-ICP-MS) was used to determine mineral/rock matrix partition coefficients for clinopyroxene and phlogopite from a Mesozoic alkaline lamprophyre.
TL;DR: It is suggested that X-MyT1 is a novel, essential element in the cascade of events that allows cells to escape lateral inhibition and to enter the pathway that leads to terminal neuronal differentiation.
TL;DR: In this article, arylsulfatase A-deficient mice were shown to exhibit a reduction of axonal cross-sectional area and an astrogliosis in 1-year-old mice; activation of microglia started at 1 year and was generalized at 2 years.
Abstract: Metachromatic leukodystrophy is a lysosomal sphingolipid storage disorder caused by the deficiency of arylsulfatase A. The disease is characterized by progressive demyelination, causing various neurologic symptoms. Since no naturally occurring animal model of the disease is available, we have generated arylsulfatase A-deficient mice. Deficient animals store the sphingolipid cerebroside-3-sulfate in various neuronal and nonneuronal tissues. The storage pattern is comparable to that of affected humans, but gross defects of white matter were not observed up to the age of 2 years. A reduction of axonal cross-sectional area and an astrogliosis were observed in 1-year-old mice; activation of microglia started at 1 year and was generalized at 2 years. Purkinje cell dendrites show an altered morphology. In the acoustic ganglion numbers of neurons and myelinated fibers are severely decreased, which is accompanied by a loss of brainstem auditory-evoked potentials. Neurologic examination reveals significant impairment of neuromotor coordination.
TL;DR: The noninvasive inclinometer technique proved to be highly reliable and valid, but the measurement technique for extension needs further refinement.
Abstract: black small square) Methods • (black small square) Results o The Inclinometer Technique With and Without Fluoroscopic Determination of Reference Points o Interrater Correlation With the Inclinometer Technique o Functional Radiography Compared With the Inclinometer