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PubMed1973

The membrane attack mechanism of complement. Verification of a stable C5-9 complex in free solution.

The membrane attack mechanism of complement, C5 to C9, has previously been postulated to associate on the target cell surface to a stable decamolecular complex with a calculated mol wt of 995,000. A soluble and stable complex consisting of C5, C6, C7, C8, and C9 has now been demonstrated to arise as a consequence of complement activation by the classical or alternate pathway. It has a sedimentation coefficient of 22.5S and a mol wt of 1 million daltons, and it migrates on electrophoresis at pH 8.6 as an alpha-globulin. The stable and soluble C5b-9 complex cannot bind to erythrocytes and has no demonstrable cytolytic activity. However, due to partially unsaturated binding sites for C9, it can bind additional C9 and thus function as an inhibitor of lysis of EAC1-8 by C9. These results support the concept according to which the membrane-bound attack system of complement represents a stable, decamolecular assembly of C5b-9. Unlike its analogue in free solution, the membrane-bound complex is cytolytically active.

Cell-Free System↗
PubMed2003

A new one-dimensional clarifier model--verification using full-scale experimental data.

A new one-dimensional clarifier model was developed, including components of existing models, and extended with a height-dependent cross-sectional area and two flowrate-dependent dispersion coefficients. This model is evaluated using data from a detailed one-month measuring campaign on a full-scale wastewater treatment plant. The data included hourly sludge concentration profile, sludge heights at 10 minute intervals, sludge concentrations in inlet, effluent and recycle flows and regular settling properties characterised by batch setting tests. Due to the poor quality concentration measurements at the surface of the clarifier, the model was not calibrated to perform well in concentration predictions at this surface. However, excellent descriptive capabilities were obtained for sludge profiles and blanket level. The Cho et al. setting velocity function was found to be significantly better in terms of description capability than the more traditional Vesilind function.

Calibration↗
PubMed2007

Predictive measures of directional benefit part 2: verification of different approaches to estimating directional benefit.

OBJECTIVE: In this investigation, the relation between various directivity measures and subject performance with directional microphone hearing aids was determined. DESIGN: Test devices included first- and second-order directional microphones. Recordings of sentences and noise (Hearing in Noise Test, HINT) were made through each test device in simple, complex, and anisotropic background noise conditions. Twenty-six subjects, with normal hearing, were administered the HINT test recordings and directional benefit was computed. These measures were correlated to theoretical, free-field, and Knowles Electronic Manikin for Acoustic Research (KEMAR) directivity index (DI) values, as well as front-to-back ratios (FBR), in situ signal-to-noise ratios (SNR), and a newly proposed Db SNR, wherein a predictive value of the SNR improvement is calculated as a function of the noise source incidence. RESULTS: The different predictive scores showed high correlation to the measured directional benefit scores in the complex (diffuse-like) background noise condition (r = 0.89 to 0.97, p < 0.05) but not across all background noise conditions (r = 0.45 to 0.97, p < 0.05). The Db SNR approach and the in situ SNR measures provided excellent prediction of subject performance in all background noise conditions (0.85 to 0.97, p < 0.05). None of the predictive measures could account for the effects of reverberation on the speech signal (r = 0.35 to 0.40, p < 0.05). CONCLUSIONS: For environments that included a discrete number of noise sources, the in situ SNR and Db SNR estimates were most predictive of subject performance. No predictive approach was indicative of the directional benefit achieved when the speech was also subjected to reverberation (temporal distortion). This finding has implications for real-world estimates of directional benefit.

Acoustics↗
PubMed2006

Deep brain stimulation for Parkinson's disease: surgical technique and perioperative management.

Deep brain stimulation (DBS) is a widely accepted therapy for medically refractory Parkinson's disease (PD). Both globus pallidus internus (GPi) and subthalamic nucleus (STN) stimulation are safe and effective in improving the symptoms of PD and reducing dyskinesias. STN DBS is the most commonly performed surgery for PD as compared to GPi DBS. Ventral intermediate nucleus (Vim) DBS is infrequently used as an alternative for tremor predominant PD patients. Patient selection is critical in achieving good outcomes. Differential diagnosis should be emphasized as well as neurological and nonneurological comorbidities. Good response to a levodopa challenge is an important predictor of favorable long-term outcomes. The DBS surgery is typically performed in an awake patient and involves stereotactic frame application, CT/MRI imaging, anatomical targeting, physiological confirmation, and implantation of the DBS lead and pulse generator. Anatomical targeting consists of direct visualization of the target in MR images, formula-derived coordinates based on the anterior and posterior commissures, and reformatted anatomical stereotactic atlases. Physiological verification is achieved most commonly via microelectrode recording followed by implantation of the DBS lead and intraoperative test stimulation to assess benefits and side effects. The various aspects of DBS surgery will be presented.

Antiparkinson Agents↗
PubMed2002

A genomics approach to the early stages of triterpene saponin biosynthesis in Medicago truncatula.

The saponins of the model legume Medicago truncatula are glycosides of at least five different triterpene aglycones: soyasapogenol B, soyasapogenol E, medicagenic acid, hederagenin and bayogenin. These aglycones are most likely derived from beta-amyrin, a product of the cyclization of 2,3-oxidosqualene. Mining M. truncatula EST data sets led to the identification of sequences putatively encoding three early enzymes of triterpene aglycone formation: squalene synthase (SS), squalene epoxidase (SE), and beta-amyrin synthase (beta-AS). SS was functionally characterized by expression in Escherichia coli, two forms of SE by complementation of the yeast erg1 mutant, and beta-AS by expression in yeast. Beta-amyrin was the sole product of the cyclization of squalene epoxide by the recombinant M. truncatulabeta-AS, as judged by GC-MS and NMR. Transcripts encoding beta-AS, SS and one form of SE were strongly and co-ordinately induced, associated with accumulation of triterpenes, upon exposure of M. truncatula cell suspension cultures to methyl jasmonate. Sterol composition remained unaffected by jasmonate treatment. Molecular verification of induction of the triterpene pathway in a cell culture system provides a new tool for saponin pathway gene discovery by DNA array-based approaches.

Acetates↗
PubMed1998

Maturation of epidermal Langerhans cells in vitro is accompanied by downregulation of 4F2 (CD98) as determined by differential display.

Following short-term culture, Langerhans cells mature morphologically and functionally into potent immunostimulatory cells. As regulation of gene expression accompanies this maturation process, it is likely that differentially expressed genes are involved in the maturation events. Using the recently described method of differential display, we generated cDNA expression patterns starting with mRNA of murine epidermal Langerhans cells isolated either directly (fLC) or following 3 d cultivation (cLC). Five hundred putative differentially expressed cDNA fragments were recovered from the gel. For a part of the fragments differential expression was confirmed by dot blot and Southern hybridization procedures. These cDNA fragments were subcloned and sequenced following the verification step. Database searches revealed that unknown genes as well as already characterized genes were identified. A cDNA fragment preferentially hybridizing with fLC was identified as the murine surface marker 4F2 (CD98). Downregulation of the activation marker 4F2/CD98 was confirmed by additional analysis at the mRNA and protein level. The downregulation of 4F2 surface expression on cLC is compatible with the notion that the committed, terminally differentiated cLC downregulate proteins involved in proliferation and cell survival.

Animals↗
PubMed2006

Electrophysiological proof of diffusion-weighted imaging-derived depiction of the deep-seated pyramidal tract in human.

In the living human brain the pyramidal tract (PT) can be displayed with magnetic resonance diffusion-weighted imaging (DWI). Although this imaging technique is already being used for planning and performing neurosurgical procedures in the PT vicinity, there is a lack of verification of DWI accuracy in other areas outside the directly subcortical PT parts. Before definitive electrode placement into the subthalamic nucleus (STN) in patients with Parkinson disease (PD) for chronic stimulation, the stimulation effect on PD symptoms and the side-effects, namely PT activation at the level of the internal capsule (IC), are electrophysiologically tested. To analyze DWI accuracy by matching the stereotactic coordinates of the electrophysiologically proven IC position with these of the DWI-derived IC display, DWI was added to the routine MRI work-up in the stereotactic frame prior to functional surgery in 6 patients. In all of the 10 displayed fiber tracts, concordant findings for imaging and macrostimulation were made. The authors proved for the first time that DWI correctly depicts the deep seated, principle motor pathways in the living human brain. Due to methodical limitations of this study the accuracy of the proven IC display is limited to 3 mm which has proven to be sufficient for the planning and performance of neurosurgical procedures in the vicinity of large fiber tracts.

Adult↗
PubMed2002

Modelling biological processes using workflow and Petri Net models.

MOTIVATION: Biological processes can be considered at many levels of detail, ranging from atomic mechanism to general processes such as cell division, cell adhesion or cell invasion. The experimental study of protein function and gene regulation typically provides information at many levels. The representation of hierarchical process knowledge in biology is therefore a major challenge for bioinformatics. To represent high-level processes in the context of their component functions, we have developed a graphical knowledge model for biological processes that supports methods for qualitative reasoning. RESULTS: We assessed eleven diverse models that were developed in the fields of software engineering, business, and biology, to evaluate their suitability for representing and simulating biological processes. Based on this assessment, we combined the best aspects of two models: Workflow/Petri Net and a biological concept model. The Workflow model can represent nesting and ordering of processes, the structural components that participate in the processes, and the roles that they play. It also maps to Petri Nets, which allow verification of formal properties and qualitative simulation. The biological concept model, TAMBIS, provides a framework for describing biological entities that can be mapped to the workflow model. We tested our model by representing malaria parasites invading host erythrocytes, and composed queries, in five general classes, to discover relationships among processes and structural components. We used reachability analysis to answer queries about the dynamic aspects of the model. AVAILABILITY: The model is available at http://smi.stanford.edu/projects/helix/pubs/process-model/.

Animals↗
PubMed2002

Theory of inert gas-condensing vapor thermoacoustics: propagation equation.

The theory of acoustic propagation in an inert gas-condensing vapor mixture contained in a cylindrical pore with wet walls and an imposed temperature gradient is developed. It is shown that the vapor diffusion effects in the mixture are analogous to the heat diffusion effects in the thermoacoustics of inert gases, and that these effects occur in parallel with the heat diffusion effects in the wet system. The vapor diffusion effects can be expressed in terms of the thermoviscous function F(lambda) used in the theory of sound propagation of constant cross-section tubes. As such, these results can be extended to any shape parallel-walled tube. The propagation equations predict that the temperature gradient required for onset of sound amplification in a wet-walled prime mover is much lower than the corresponding temperature gradient for an inert gas prime mover. The results of a measurement of the onset temperature of a simple demonstration prime mover in air with a dry stack and with a stack wetted with water provide a qualitative verification of the theory.

Models, Theoretical↗
PubMedDate not supplied

[Additional limitations of the Shrikhande method and their verification].

Shrikhande's method was checked on linear-variety common wheat Lutescens 62. Two causes for a distortion of the ratio of genotypic and paratypic components of the variance were established: parameter b of Smith's law is not constant for a given field and depends on the method of parcelling: Smith's law is not confirmed at all. A two-stage test of Shrikhande's method correctness is suggested for checking its limitations in practice. The analysis of variance for any given parcelling is done at the first stage. Significant ratios of between-cluster mean squares and within-cluster mean squares indicate that Smith's law is confirmed. The second stage consists in the analysis of variance of lg V(X) linear regression by lg X or in the graphical analysis of the function lg V(X) = = f (lg X).

Genetic Techniques↗
PubMed1983

'Frustration--anxiety behaviour as a function of leprosy patients age and personality'.

The paper incorporates five studies (i.e., four of frustration and one of anxiety). The design is 'Multi-group-Control-group'. Each one of the five studies has four '3 X 3 X 2' factorial experiments. Each experiment has 360 elements. These are three groups (of lepromatous, non-lepromatous and of disease-free normals). Each group consists of 120 elements (equally distributed among adolescents, adults and senescents). The particulars of the patients have been obtained from the Central JALMA Institute for Leprosy and the Kushta Seva Sadan (Agra). The disease-free normal elements are drawn freely from the population of the Agra town. The sample possesses statistical justification for size and representativeness. Data are collected with the help of reliable tools and the 'F' test is run for verification of the 'null hypotheses'. Results show that experiences of 'fixation-regression' frustration, atypically belong to normal senescence. Resignation and anxiety experiences, as growing hazards, specifically relate to leprosy patients. Personality factors that normally demote 'frustration-anxiety' behaviour exhibit 'role-negation' in the leprosy patients. Age shows 'role-reversion'. Implications of such 'role' changes relate to the 'self-eroding' process of personality in the patients.

Adolescent↗
PubMed1984

Neuropsychological analysis of a case of crossed dysphasia verified at postmortem.

A case is reported of crossed dysphasia in a right-handed monolingual patient, where neuropathological verification of the unilateral site of the lesion was obtained within a year of detailed neuropsychological assessment. The patient's pattern of language impairment was characterized by agrammatic speech and relatively preserved naming ability. In addition, the patient had good repetition, poor comprehension, and marked impairment on visuospatial tasks. Neuropathological investigations showed a large area of infarction affecting cortex, white matter, and subcortical structures in the right hemisphere. The possibility is discussed of a distinction between two types of crossed dysphasia with either dissociated or simultaneous language and visuospatial deficits due to reversed representation of hemispheric specific functions or transfer of most cognitive functions to the right hemisphere.

Aphasia↗
PubMed2006

In silico modelling of hormone response elements.

BACKGROUND: An important step in understanding the conditions that specify gene expression is the recognition of gene regulatory elements. Due to high diversity of different types of transcription factors and their DNA binding preferences, it is a challenging problem to establish an accurate model for recognition of functional regulatory elements in promoters of eukaryotic genes. RESULTS: We present a method for precise prediction of a large group of transcription factor binding sites - steroid hormone response elements. We use a large training set of experimentally confirmed steroid hormone response elements, and adapt a sequence-based statistic method of position weight matrix, for identification of the binding sites in the query sequences. To estimate the accuracy level, a table of correspondence of sensitivity vs. specificity values is constructed from a number of independent tests. Furthermore, feed-forward neural network is used for cross-verification of the predicted response elements on genomic sequences. CONCLUSION: The proposed method demonstrates high accuracy level, and therefore can be used for prediction of hormone response elements de novo. Experimental results support our analysis by showing significant improvement of the proposed method over previous HRE recognition methods.

Binding Sites↗
PubMed1997

[Point mutations of the thyrotropin receptor gene in autonomously functioning thyroid gland nodules: correlation with clinical findings and morphology].

Seventeen autonomously functioning thyroid nodules (AFTN) were analyzed for the most frequent mutations of the thyrotropin (TSH) receptor gene at codons 619, 631, 632 and 633. DNA was extracted from formalin-fixed, paraffin-embedded samples from both nodules and surrounding tissue after micro- or macrodissection. A fragment of the TSH receptor gene (bp 1762-1976) encoding the third cytoplasmic loop and the sixth transmembranous domain was amplified by PCR. Screening for mutations at codons 619, 631, 632 and 633 was performed by restriction enzyme analysis using Asp 718, Hph I, Taq I and EcoR I, respectively. For verification, cases with a mutated restriction site were cloned and sequenced. Mutations were found in 3 AFTNs (18%): in 2 cases at codon 632 and in 1 case at codon 631. The 2 cases with a mutation at codon 632 harbored additional mutations at codon 599 and 640, respectively, detected by sequencing. Normal thyroid tissue outside the AFTNs did not harbor mutant TSH-receptor. Mutations occurred in patients with clinical and subclinical hyperthyroidism. Mutations were associated both with total (2 cases) and partial (1 case) suppression of the surrounding thyroid tissue as noted on the scinti scan. AFTNs with TSH-receptor mutation occurred as single nodules. All 3 nodules with mutations were classified histologically as nodular hyperplasia according to the criteria of the WHO. Although the number of cases is small, our data suggest that AFTNs are clinically and morphologically heterogenous. Since the most common TSH-receptor mutations occur only in a small subset of AFTNs other molecular genetic alterations may be involved in the development of AFTNs.

Adenoma↗
PubMed1992

How little luteal tissue of rats is needed to maintain pregnancy till term--an experimental verification.

Surgical reduction of luteal tissue to about 20% of its total mass on day 5 pc was found to maintain gestation till term. A high degree of fetal loss was, however, evident. An identical surgical manipulation at the end of maximal luteal maturity, that is, on day 16 pc, resulted in normal maintenance of gestation. Fetal growth and their survival rate were found to be comparable to controls. An exclusive surgical extirpation of corpora lutea, on the other hand, either on day 16, 17, 18 or 19 was found to cause 100% fetal loss by day 23. However, progesterone replacement therapy concurrently with surgical luteal ablation till day 20, or surgical extirpation of the entire luteal mass when shifted on day 20, led the pregnancy to term. Present experimental findings, therefore, suggest that only about 20% of the functionally matured luteal mass until day 20 is essentially enough to maintain an ideal pregnancy status till term.

Animals↗
PubMed1978

Heterogeneity of human alpha-fetoprotein as revealed by isoelectric focusing in urea-containing gels.

The heterogeneity of human alpha-fetoprotein has been studied by analytical isoelectric focusing in polyacrylamide gel slabs in the presence of 8 M urea. Six major isoelectric variants could be identified over a pH range of 6.0--6.2. Verification of their identity was achieved by crossed immunoelectrophoresis into agarose gel containing monospecific antiserum to human alpha-fetoprotein. Complete desialylation of the protein did not abolish the heterogeneity; a complex pattern of major alpha-fetoprotein bands persisted over a more alkaline pH range. We have been able to correlate the pattern of alpha-fetoprotein heterogeneity seen following extended agarose gel electrophoresis with that obtained during isoelectric focusing in the presence of urea. The quantity of certain alpha-fetoprotein charge isomers in various alpha-fetoprotein isolates may be important in considering certain biological functions of this protein.

Carcinoma, Hepatocellular↗
PubMed2002

[Data bank project for acute stroke patients].

Stroke is the second cause of death within major adult disease and the first cause of functional disability for elderly in Japan. The diffusion rate of MRI is the highest in the world. Even though, there is only few evidence for stroke management has been reported from Japan. It is necessary to make a data bank of acute stroke patients as infrastructure making evidence for standardization of stroke management. We made Japan standard stroke registry study supported by ministry of health and welfare for 3 years. We completed computerized registry system and accumulated about 8,000 acute stroke cases from 45 stroke center hospitals. This system is also functioning as a stroke database for each hospital. From the analysis of the distribution of stroke subtype, the incidence of atherothrombotic infarction and cardiogenic embolism was similar to lacunar infarction as shown in Fig. 1. Furthermore, the 38% of ischemic stroke patients admitted within 3 hours. Thrombolytic therapy was performed in 15% of the patients who admitted within 3 hours and their initial severity were NIHSS 6-29. The outcome of the patients treated with thrombolytic therapy was significantly better than those without it. These data indicate that the stroke data bank should be useful tool to make verification of the guideline and planning of clinical trial for EBM.

Acute Disease↗
PubMed1988

[The function of the reticuloendothelial system studied with the use of radioactive colloids].

A new method for the interpretation of data obtained during radionuclide investigation of the reticuloendothelial system (RES) was proposed. It was based on a detailed description of the mechanism of reticuloendothelial extraction of a colloid injected intravenously. A model developed for this purpose included the main stages of radioactive colloid transport. The paper also represented a comparative analysis of the results of clinical examination of the controls and patients with liver cirrhosis. A 4-fold decrease of the blood flow in portal liver cirrhosis was noted as compared with normal mean indices in a 2-fold decrease in the specific blood supply of cells of the RES and in a 2-fold decrease in its volume. An increase in phagocytosis rate in patients with liver cirrhosis needs further verification.

Algorithms↗