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PubMed1997

A stereological method for estimating the total length and size of myelin fibers in human brain white matter.

A practically unbiased stereological method to obtain estimates of the volume and total length of nerve fibers in brain white matter is described. The sampling scheme is designed so that the majority of brain white matter is left intact, thus providing the possibility for resampling and further analysis. Uniform sampling of one complete hemispherical white matter is performed. The volume fraction of nerve fibers in white matter is estimated by point counting. The total length of nerve fibers was estimated from the product of the volume of white matter, obtained with the Cavalieri principle, and the fiber length density, obtained from the isotropic, uniform random sections which were ensured by the isector. The size of nerve fibers was derived by measuring the profile diameter perpendicular to its longest axis. The influence of the postmortem fixation delay on nerve fiber parameters was investigated in one dog and one pig. The criteria for identification of nerve fiber profiles at light microscopy were evaluated using electron microscopy.

Adolescent↗
PubMed2001

Purification and catalytic properties of the chlorophenol 4-monooxygenase from Burkholderia cepacia strain AC1100.

Burkholderia cepacia strain AC1100 can be induced for the degradation of 2,4,5-trichlorophenol (2,4,5-TCP). We have purified the active enzyme 30-fold to apparent homogeneity with a 44% yield by a two-step chromatographic procedure, and showed that it consists of a single type of subunit of 59 kDa based on SDS-PAGE using Coomassie blue and Sypro staining. This enzyme has no bound prosthetic group but requires exogenous addition of FAD and NADH to perform the dioxygen-dependent hydroxylation in the 4-position of 2,4,6-TCP. Studies of the stoichiometry revealed the consumption of 2 mol of NADH plus 1 mol of dioxygen per mol of 2,4,6-TCP with identification of the reaction product as 2,6-dichlorohydroquinone. Steady state kinetic parameters for cofactors and a variety of substrates were determined. Low K(m) values of 1+/-0.1 microM, 32+/-5 microM and 4+/-2 microM were found for FAD, NADH and 2,6-dichlorophenol (2,6-DCP), respectively, under saturating conditions for the two others. In the presence of 2,6-DCP as a substrate, methimazole (MMI) inhibited the enzyme competitively with a K(i)=27 microM. When other polychlorinated substrates were studied, IC(50) values for MMI were found in a range compatible with their apparent affinity. On the basis of aromatic product formation, NADH and O(2) consumption schemes for 2,4,6-TCP and 2,4,5-TCP degradation are discussed. A Blast search revealed that this enzyme has a high sequence identity (60%) with 2,4,6-TCP-4-monooxygenases from Burkholderia pickettii and from Azotobacter sp. strain GP1 which all of them catalyze para hydroxylative dehalogenation.

Burkholderia cepacia↗
PubMed1997

Parametric (integrated backscatter and attenuation) images constructed using backscattered radio frequency signals (25-56 MHz) from human aortae in vitro.

Quantitative ultrasonic tissue characterization using backscattered high-frequency intravascular ultrasound could provide a basis for the objective identification of lesions in vivo. Representation of local measurements of quantitative ultrasonic parameters in a conventional image format should facilitate their interpretation and thus increase their clinical utility. Toward this goal, the apparent integrated backscatter, the slope of attenuation (25-56 MHz) and the value of the attenuation on the linear fit at 37.5 MHz were measured using the backscattered radio frequency signals from in vitro human aortae. Local estimations of these ultrasonic parameters from both normal and atherosclerotic aortic segments were displayed in a B-scan format. The morphological features of these parametric images corresponded well to features of histological images of the same regions. The attenuation from 25-56 MHz of seven segments of the medial layer (both with and without overlying atheroma) were measured using the multinarrow-band backscatter method. The average attenuation in the media at 24 degrees C +/- 3 degrees C was 45 +/- 16 dB/cm at 25 MHz and 102 +/- 13 dB/cm at 50 MHz. This work represents progress toward the development of quantitative imaging methods for intravascular applications.

Aorta, Thoracic↗
PubMed2003

Substituted 2-pyridinemethanol derivatives as potent and selective phosphodiesterase-4 inhibitors.

The synthesis and the phosphodiesterase-4 (PDE4) inhibitory activity of 2-pyridinemethanol derivatives is described. The evaluation of the structure-activity relationship (SAR) in this series of novel PDE4 inhibitors led to the identification of compound 9 which exhibits excellent in vitro activity, desirable pharmacokinetic parameters and good efficacy in animal models of bronchoconstriction.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

Solution structure and backbone dynamics of the photoactive yellow protein.

The solution structure of photoactive yellow protein (PYP), a photosensory protein from Ectothiorhodospira halophila, has been determined by multidimensional NMR spectroscopy. The structure consists of an open, twisted, 6-stranded, antiparallel beta-sheet, which is flanked by four alpha-helices on both sides. The final set of 26 selected structures is well-defined for the regions spanning residues Phe6-Ala16, Asp24-Ala112, and Tyr118-Val125 and displays a root-mean-square deviation, versus the average, of 0.45 A for the backbone and 0.88 A for all heavy atoms. Comparison of the solution structure with an earlier published 1.4 A crystal structure (Borgstahl, G. E. O., Williams, D. R., and Getzoff, E. D. (1995) Biochemistry 34, 6278-6287) reveals a similarity with a root-mean-square deviation of 1.77 A for the backbone for the well-defined regions. The most distinct difference in the backbone with the crystal structure is found near the N-terminus, for residues Asp19-Leu23, which corresponds to an alpha-helix in the crystal structure and to one of the poorest defined regions in the solution structure. To characterize the dynamic behavior of PYP in solution, we undertook a 15N relaxation study and measurements of hydrogen/deuterium exchange. Determination of order parameters through the model-free Lipari-Szabo approach enabled the identification of several regions of enhanced dynamics. The comparison of atomic displacements in the backbone traces of the ensemble structures, with mobility measurements from NMR, show that the poorly defined regions feature fast internal motions in the nanosecond to picosecond time scale.

Bacterial Proteins↗
PubMed2003

Use of multiwavelength transmission spectroscopy for the characterization of Cryptosporidium parvum oocysts: quantitative interpretation.

Combined scattering and absorption properties of suspended particles can be obtained as a function of wavelength by measuring the complete ultraviolet-visible (UV-vis) spectrum. This research reports on the quantitative interpretation of measured UV-vis spectra of Cryptosporidium parvum oocyst suspensions obtained from several commercial sources and evaluated using two different purification techniques. The reproducibility of the measured spectral data was assessed, and the quantitative interpretation of the oocyst spectra in terms of the particle size and the chemical composition of the particles are reported herein. The interpretation model of the spectra is based on light scattering theory, spectral deconvolution techniques, and on the approximation of the wavelength-dependent optical properties of the basic constituents of living organisms. A characteristic set of optical properties for C. parvum oocysts has been determined as a function of wavelength and used for the quantitative interpretation of UV-vis spectra. The results from the spectral deconvolution show quantitative differences among oocyst preparations. These results represent the first step in establishing a set of critical parameters (e.g., oocyst size and chemical composition) necessary for the detection and identification of C. parvum oocysts in water using spectroscopy.

Animals↗
PubMed2006

Comparison of vacuum matrix-assisted laser desorption/ionization (MALDI) and atmospheric pressure MALDI (AP-MALDI) tandem mass spectrometry of 2-dimensional separated and trypsin-digested glomerular proteins for database search derived identification.

Mass spectrometric based sequencing of enzymatic generated peptides is widely used to obtain specific sequence tags allowing the unambiguous identification of proteins. In the present study, two types of desorption/ionization techniques combined with different modes of ion dissociation, namely vacuum matrix-assisted laser desorption/ionization (vMALDI) high energy collision induced dissociation (CID) and post-source decay (PSD) as well as atmospheric pressure (AP)-MALDI low energy CID, were applied for the fragmentation of singly protonated peptide ions, which were derived from two-dimensional separated, silver-stained and trypsin-digested hydrophilic as well as hydrophobic glomerular proteins. Thereby, defined properties of the individual fragmentation pattern generated by the specified modes could be observed. Furthermore, the compatibility of the varying PSD and CID (MS/MS) data with database search derived identification using two public accessible search algorithms has been evaluated. The peptide sequence tag information obtained by PSD and high energy CID enabled in the majority of cases an unambiguous identification. In contrast, part of the data obtained by low energy CID were not assignable using similar search parameters and therefore no clear results were obtainable. The knowledge of the properties of available MALDI-based fragmentation techniques presents an important factor for data interpretation using public accessible search algorithms and moreover for the identification of two-dimensional gel separated proteins.

Algorithms↗
PubMed2005

[Investigation of the rhythmical embrocating according to Wegman/Hauschka].

INTRODUCTION: With the research on Rhythmical Embrocating according to Wegman/Hauschka (RE) since the 1990ies, nursing science has made an important contribution in obtaining acceptance for complementary methods. AIM, MATERIAL AND METHODS: Based on methods of phenomenology of the living body inspired by Goethean science, we aimed to investigate on the following question: What are the typical psychosomatic reactions of patients treated with RE? Theoretical sampling led to the inclusion of 13 nursing experts on RE. RESULTS: We found three typical pattern of patient-reaction on RE: being uncaged - re-identifing - empowering. These patterns do not only rely on changes of physical parameters, but also suggest changes of vegetative, mental and spiritual dimensions. CONCLUSION: A careful interpretation of our results leads to the conclusion, that the concepts derived here might be seen as archetypes of human reaction on specific kinds of therapeutic touch.

Complementary Therapies↗
PubMedDate not supplied

Recent advances in immunosuppressive therapy for renal transplantation.

Recent advances in immunosuppression have focused on more effective, safer, and targeted therapies that have resulted in improved short- and intermediate-term renal allograft survival. During the past decade there has been a marked decrease in acute rejection rates following renal transplantation because of the use of newer immunosuppressive agents. Recent data indicate that the average yearly reduction in the relative hazard of graft failure beyond 1 year was 4.2% for all recipients (0.4% for those recipients who had an acute rejection episode and 6.3% for those who did not have an acute rejection). Despite these improvements the currently available immunosuppressive agents are associated with significant cardiovascular risk factors, an increased risk of infection, and the development of malignancies in the long term. Predictive parameters of donor-specific hyporesponsiveness are needed so as to allow identification of patients in whom immunosuppressive therapy can be safely reduced. Immunosuppressive agents that have recently been approved for use in the United States and those that are in clinical and preclinical studies are discussed.

Animals↗
PubMed1991

A clinical cancer prevention curriculum in a comprehensive cancer center.

Interns, residents, and medical students who spend one month at a comprehensive cancer center are presented with a strategy to incorporate cancer preventive services into their outpatient practices. This is accomplished through didactic lectures in clinical epidemiology. Terms that are essential to an understanding of disease occurrence are defined including incidence, prevalence, and mortality rate. Odds and probability are explored with the introduction of the odds ratio and the identification of risk factors. Primary and secondary cancer prevention are defined, and parameters related to cancer screening are introduced (sensitivity, specificity, prevalence, and positive predictive value). Risk factors for malignancy are identified where they are known and can be modified. Primary prevention strategies are reviewed by site along with data that support or refute recommendations for site-specific screening. Medical conditions and risk factor profiles that define high-risk groups are reviewed. Trainees are given copies of the US Preventive Services Task Force screening recommendations and a clinical handbook. The impact of this information on clinical practice patterns remains to be evaluated.

Cancer Care Facilities↗
PubMed2025

qcCHIP: an R package to identify clonal hematopoiesis variants using cohort-specific data characteristics.

SUMMARY: Clonal hematopoiesis (CH) is a molecular biomarker associated with various adverse outcomes in both healthy individuals and those with underlying conditions, including cancer. Detecting CH usually involves genomic sequencing of individual blood samples followed by robust bioinformatics data filtering. We report an R package, qcCHIP, a bioinformatics pipeline that implements permutation-based parameter optimization to guide quality control filtering and cohort-specific CH identification. We benchmark qcCHIP under various data settings, including different sequencing depths, ranges of cohort sizes, with and without normal-tumor paired samples, and across different cancer types. We show that qcCHIP allows users to customize analysis needs to generate CH calls based on cohort-specific data characteristics. AVAILABILITY AND IMPLEMENTATION: qcCHIP R package is freely accessible at GitHub https://github.com/tenglab/qcCHIP and DOI: 10.5281/zenodo.16421861.

Humans↗
PubMed1988

Sonographic diagnosis of fetal growth disorders.

In summary, accurate identification of fetal growth disorders remains a difficult clinical challenge. Many diagnostic parameters have been devised to diagnose these conditions, however, no single test alone allows a confident antenatal diagnosis of IUGR or macrosomia to be established. Until new criteria or new methods such as Doppler analysis of umbilical artery flow permit a more accurate prediction of growth disturbances, multiple parameters should be monitored. Evaluation of the amniotic fluid volume, BPD, FL, AC, and EFW should be included in all studies. In high risk cases (unexplained oligohydramnios, previous history of growth retardation, poor nutritional status, abnormal sonographic parameters, maternal obesity, diabetes mellitus, etc.) additional measurements such as the HC/AC ratio and the FL/AC ratio should also be evaluated. Similarly, evaluation of suspected excessive fetal growth requires careful evaluation of AC measurements. Patients with suspected growth disorders should be reevaluated with serial scans at 2 to 3 weeks intervals. Careful monitoring of fetuses with suspected IUGR and macrosomia may decrease much of the morbidity and mortality associated with these conditions.

Amniotic Fluid↗
PubMed2000

Important issues in occupational asthma.

Although there has been a dramatic increase in awareness about the contributions of the work environment to asthma, many aspects of this illness remain to be explored in further detail. This article focuses on issues that need to be better understood. Data are reported that describe newly recognized agents in the workplace that have been shown in a sophisticated manner to induce asthma. In addition, data that further describe the mechanisms of occupational asthma and information regarding the management of occupational asthma are given. Important problems yet to be resolved include whether those who develop occupational asthma from different agents are likely to have different outcomes, whether screening is likely to have a significant effect on the outcome (and, if so, what is the best approach to screening), and identification of a clear definition of the role of immunologic-mediated parameters as they relate to the initiation of asthma attributable to low molecular weight agents and patient outcome. There is little information about "safe" levels of exposure that protect all workers. Data (such as underlying specific immunologic or genetic markers) are lacking that might aid in predicting which workers are likely to be sensitized by low molecular weight agents. This abbreviated list of unresolved issues makes the study of occupational asthma a fertile field for research.

Air Pollutants, Occupational↗
PubMed2003

Prolongation of the QT-corrected interval during dobutamine stress echocardiography: a marker for ischemia.

BACKGROUND: Dobutamine stress echocardiography (DSE) has become a very reliable non-invasive tool in the diagnosis of ischemic heart disease based on the determination of new wall motion abnormalities rather than electrocardiographic changes. METHODS: In this study, we assessed the usefulness of the corrected QT (QTc) interval and delayed heart rate recovery in predicting ischemia during the infusion of dobutamine. In this retrospective analysis, we analyzed the electrocardiograms of 100 patients who underwent DSE for the diagnosis of coronary artery disease. The QTc interval obtained at peak heart rate during the infusion of dobutamine was compared with the QTc interval at rest. RESULTS: A total of 32 patients had new wall motion abnormalities during DSE, suggestive of ischemia. In these patients, the mean QTc interval at rest was 442.6 ms as compared to 461.0 ms during the peak infusion of dobutamine (P<0.05). In contrast, there was no statistical difference between the mean QTc interval at rest and that noted during DSE in patients without ischemia (439.8 ms and 440.1 ms respectively, P =ls; NS). The QTc interval increased in 40% of patients with ischemia on DSE despite the absence of any accompanying ST-segment depressions. In addition, there was a statistically slower heart rate recovery. Changes in heart rate 2 min into recovery from peak heart rate were 7.3+/-9.5 beats/min in patients with ischemia compared to 12.5+/-11.9 beats/min in those without ischemia (P<0.027). A more significant change was noted 4 min into recovery when compared with the peak heart rate, 14.8+/-10 beats/min in patients with ischemia, compared with 22.2+/-15.7 beats/min in those without ischemia, (P<0.007). CONCLUSIONS: These results suggest that the development of new wall motion abnormalities suggestive of ischemia during DSE is associated with prolongation of the QTc interval and delayed heart rate early in the recovery period. These two parameters should be further studied not only as additional markers in the identification of ischemia in patients referred for DSE but also to assess their potential significance during short- and long-term follow-up.

Aged↗
PubMed1996

An efficient approach to ARMA modeling of biological systems with multiple inputs and delays.

This paper presents a new approach to AutoRegressive Moving Average (ARMA or ARX) modeling which automatically seeks the best model order to represent investigated linear, time invariant systems using their input/output data. The algorithm seeks the ARMA parameterization which accounts for variability in the output of the system due to input activity and contains the fewest number of parameters required to do so. The unique characteristics of the proposed system identification algorithm are its simplicity and efficiency in handling systems with delays and multiple inputs. We present results of applying the algorithm to simulated data and experimental biological data In addition, a technique for assessing the error associated with the impulse responses calculated from estimated ARMA parameterizations is presented. The mapping from ARMA coefficients to impulse response estimates is nonlinear, which complicates any effort to construct confidence bounds for the obtained impulse responses. Here a method for obtaining a linearization of this mapping is derived, which leads to a simple procedure to approximate the confidence bounds.

Algorithms↗
PubMed2003

Autonomous system for Web-based microarray image analysis.

Software-based feature extraction from DNA microarray images still requires human intervention on various levels. Manual adjustment of grid and metagrid parameters, precise alignment of superimposed grid templates and gene spots, or simply identification of large-scale artifacts have to be performed beforehand to reliably analyze DNA signals and correctly quantify their expression values. Ideally, a Web-based system with input solely confined to a single microarray image and a data table as output containing measurements for all gene spots would directly transform raw image data into abstracted gene expression tables. Sophisticated algorithms with advanced procedures for iterative correction function can overcome imminent challenges in image processing. Herein is introduced an integrated software system with a Java-based interface on the client side that allows for decentralized access and furthermore enables the scientist to instantly employ the most updated software version at any given time. This software tool is extended from PixClust as used in Extractiff incorporated with Java Web Start deployment technology. Ultimately, this setup is destined for high-throughput pipelines in genome-wide medical diagnostics labs or microarray core facilities aimed at providing fully automated service to its users.

Algorithms↗
PubMed1997

Anatomy of the cranioencephalic structures of the goat (Capra hircus L.) by imaging techniques: a computerized tomographic study.

A topographic study of the cranioencephalic structure was carried out by computerized tomography on Canarian breed adult goats of medium size and weight, with similar cephalic parameters. In this way, transversal, sagittal and horizontal tomographic images were obtained. Identification of the observed anatomic structures represents the basis of this work from which applicable specie data are derived.

Animals↗
PubMed1994

MRI-based hippocampal volume measurements in epilepsy.

In the study of brain morphometry, it is accepted that a relationship exists between brain structure and function, both normal and abnormal. One descriptor of morphometric structure is volume. Abnormalities in hippocampal morphology, including unilateral or bilateral volume loss, are known to occur in epilepsy, Alzheimer's disease, and in certain amnestic syndromes. Precise quantitation should improve understanding of the role of any biologic system in normal function and in disease. The objectives of magnetic resonance (MR)-based hippocampal volume measurements are precise quantitation, identification of a normal range, and identification of the association between biologic variables and aberrations in this volumetric parameter. Volumetric measures introduce a level of precision in the estimation of hippocampal size that is not available simply by visually inspecting a set of MR images, thus enabling statistically based hypothesis testing. To produce accurate hippocampal volume measurements with magnetic resonance imaging (MRI), attention must be directed to the two major components of the operation as a whole, MR image acquisition and image processing.

Atrophy↗