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PubMedDate not supplied

Localization of a sequence motif complementary to the nuclear localization signal in proteasomes from Thermoplasma acidophilum by immunoelectron microscopy.

A sequence motif complementary to the nuclear localization signal (NLS) has been localized in proteasomes from Thermoplasma acidophilum by immunoelectron microscopy using sequence-specific antibodies. The antibodies were generated in two different ways: by immunization with a carrier-coupled peptide and by isolation of the sequence-specific antibody from an immune serum against native proteasomes using a peptide-affinity column. The sequence specificity of the isolated antibody was confirmed by a PEPSCAN-ELISA performed on overlapping nonapeptides deduced from the sequence of the alpha-subunit of the Thermoplasma proteasome. Compared to the antibody induced by the carrier-coupled peptide this antibody fraction showed a much higher affinity for native proteasomes. The attachment site of the Fab portion of the antibody to the proteasome was mapped by electron microscopy in conjunction with image processing. The antibody was found to bind to the periphery of the two outer "disks" of the proteasome complex formed by the alpha-subunits.

Amino Acid Sequence↗
PubMedDate not supplied

Calcium signaling mechanisms in the gastric parietal cell.

Gastric hydrochloric acid (HCl) secretion is stimulated in vivo by histamine, acetylcholine, and gastrin. In vitro studies have shown that histamine acts mainly via a cAMP-dependent pathway, and acetylcholine acts via a calcium-dependent pathway. Histamine also elevates intracellular calcium ([Ca2+]i) in parietal cells. Both gastrin and acetylcholine release histamine from histamine-containing cells. In humans, rats, and rabbits, there is considerable controversy as to whether or not gastrin receptors are also present on the parietal cell. We utilized digitized video image analysis techniques in this study to demonstrate gastrin-induced changes in intracellular calcium in single parietal cells from rabbit in primary culture. Gastrin also stimulated a small increase in [14C]-aminopyrine (AP) accumulation, an index of acid secretory responsiveness in cultured parietal cells. In contrast to histamine and the cholinergic agonist, carbachol, stimulation of parietal cells with gastrin led to rapid loss of the calcium signaling response, an event that is presumed to be closely related to gastrin receptor activation. Moreover, different calcium signaling patterns were observed for histamine, carbachol, and gastrin, Previous observations coupled with present studies using manganese, caffeine, and ryanodine suggest that agonist-stimulated increases in calcium influx into parietal cells do not occur via voltage-sensitive calcium channels or nonspecific divalent cation channels. It also appears to be unlikely that release of intracellular calcium is mediated by a muscle or neuronal-type ryanodine receptor. We hypothesize that calcium influx may be mediated by either a calcium exchange mechanism or by an unidentified calcium channel subtype that possesses different molecular characteristics as compared to muscle, nerve, and certain secretory cell types such as, for example, the adrenal chromaffin cell. Release of intracellular calcium may be mediated via both InsP3-sensitive and -insensitive mechanisms. The InsP3-insensitive calcium pools, if present, do not appear, however, to possess ryanodine receptors capable of modulating calcium efflux from these storage sites.

Aminopyrine↗
PubMed1976

Suggested minimum performance characteristics of data acquisition instrumentation in computer-assisted ECG processing systems.

The increasing importance of electrocardiogram (ECG) interpretation by computers warrants consideration of the specific technical requirements for ECG recorders used in computer-assisted ECG interpretation systems. An almost uniform characteristic of these devices is their capability to transmit the ECG signal over common carrier lines. This paper suggests minimum performance characteristics for the different components of a teletransmitting ECG recorder to facilitate the use and evaluation of computer-assisted interpretation systems. Considered are the need for signal fidelity, features for automatic quality control, and features for patient and technician safety. The performance characteristics for the ECG amplifier are only stated where they exceed the most recent recommendations of the Committee on Electrocardiography, American Heart Association. The features of the teletransmission section are based on a widely used mode and format of transmission.

Amplifiers, Electronic↗
PubMedDate not supplied

Atrial electrogram monitoring in a cardiac care unit.

Routine monitoring of a bipolar atrial electrogram (AEG) simultaneously with the electrocardiogram is a useful and safe clinical technique for the diagnosis of complex cardiac dysrhythmias. The large-amplitude A waves of the AEG can be more reliably identified than the corresponding low-amplitude p waves of the electrocardiogram. Epicardial wires placed during cardiac surgery, catheter-mounted endocardial electrodes, and esophageal electrodes can all be used for routine AEG monitoring. A multipurpose pulmonary arterial catheter with a pair of electrodes, and esophageal electrodes can all be used for routine AEG monitoring. A multipurpose pulmonary arterial catheter with a pair of electrodes mounted on the proximal shaft can be used for combined AEG and hemodynamic monitoring. The equipment needed for AEG monitoring and recording consists of an additional bedside amplifier with 12- to 100-Hz band-pass filter, a dual-channel display scope, and a dual-channel strip chart recorder. Care must be used to keep the atrial electrodes electrically isolated for patient safety. In addition to enhancing the diagnosis and management of dysrhythmias, recording an AEG provides a signal that is suitable for automatic processing.

Arrhythmias, Cardiac↗
PubMed2021

Epigenetically regulated digital signaling defines epithelial innate immunity at the tissue level.

To prevent damage to the host or its commensal microbiota, epithelial tissues must match the intensity of the immune response to the severity of a biological threat. Toll-like receptors allow epithelial cells to identify microbe associated molecular patterns. However, the mechanisms that mitigate biological noise in single cells to ensure quantitatively appropriate responses remain unclear. Here we address this question using single cell and single molecule approaches in mammary epithelial cells and primary organoids. We find that epithelial tissues respond to bacterial microbe associated molecular patterns by activating a subset of cells in an all-or-nothing (i.e. digital) manner. The maximum fraction of responsive cells is regulated by a bimodal epigenetic switch that licenses the TLR2 promoter for transcription across multiple generations. This mechanism confers a flexible memory of inflammatory events as well as unique spatio-temporal control of epithelial tissue-level immune responses. We propose that epigenetic licensing in individual cells allows for long-term, quantitative fine-tuning of population-level responses.

Animals↗
PubMed1976

International standard (C.C.I.T.T.) for transmitting biomedical analogue and digital data on the public telephone network.

Analogue transmission of biomedical signals over the public telephone network has advantages from the economic point of view over digitalized transmission. This paper deals with the special problems encountered with the transmission of biomedical signals. Furthermore, the new international transmission standard C.C.I.T.T. recommendation V. 16 is introduced. This standard has recently been adopted by the relevant study group and has been presented to the Plenary Assembly of the C.C.I.T.T. for final approval. This standard is compatible with the existing public telephone networks. The technical specifications of this standard allow the transmission of the three-channel ECG for diagnostic purposes, e.g., remote processing and computer-assisted evaluation, as well as the transmission of the one-channel ECG with acoustic coupling, e.g., in emergency cases and for pace maker monitoring.

Analog-Digital Conversion↗
PubMed1992

Intercellular calcium signaling via gap junctions in glioma cells.

Calcium signaling in C6 glioma cells in culture was examined with digital fluorescence video microscopy. C6 cells express low levels of the gap junction protein connexin43 and have correspondingly weak gap junctional communication as evidenced by dye coupling (Naus, C. C. G., J. F. Bechberger, S. Caveney, and J. X. Wilson. 1991. Neurosci. Lett. 126:33-36). Transfection of C6 cells with the cDNA encoding connexin43 resulted in clones with increased expression of connexin43 mRNA and protein and increased dye coupling, as well as markedly reduced rates of proliferation (Zhu, D., S. Caveney, G. M. Kidder, and C. C. Naus. 1991. Proc. Natl. Acad. Sci. USA. 88:1883-1887; Naus, C. C. G., D. Zhu, S. Todd, and G. M. Kidder. 1992. Cell Mol. Neurobiol. 12:163-175). Mechanical stimulation of a single cell in a culture of non-transfected C6 cells induced a wave of increased intracellular calcium concentration ([Ca2+]i) that showed little or no communication to adjacent cells. By contrast, mechanical stimulation of a single cell in cultures of C6 clones expressing transfected connexin43 cDNA induced a Ca2+ wave that was communicated to multiple surrounding cells, and the extent of communication was proportional to the level of expression of the connexin43 cDNA. These results provide direct evidence that intercellular Ca2+ signaling occurs via gap junctions. Ca2+ signaling through gap junctions may provide a means for the coordinated regulation of cellular function, including cell growth and differentiation.

Calcium↗
PubMed2026

Striping artifact removal in VisiumHD data through nuclear counts modeling.

MOTIVATION: 10x Genomics VisiumHD enables spatial transcriptomics at 2 µm × 2 µm resolution but exhibits slide-specific, non-periodic striping artifacts due to lane-width variability. These multiplicative row/column effects distort bin total counts and can bias downstream analyses. The state-of-the-art destriping approach is the normalization procedure used as a preprocessing step in bin2cell; it applies sequential high-quantile row- then column-wise normalization, which is asymmetric and can introduce edge effects/macro-stripes and distortions of large-scale total-count structure. RESULTS: We propose a statistical destriping approach that leverages nuclei segmentation from the co-registered H&E image. Assuming transcript abundance is constant within each nucleus, we model bin counts with a negative binomial distribution whose mean is a product of a nucleus-specific concentration and row- and column-specific stripe-factors reflecting lane-width variation. We fit all parameters in a generalized linear modeling framework with cross-validated regularization on stripe-factors and iterative dispersion estimation, and use the fitted parameters to correct the observed counts into a destriped image. On synthetic data with known ground truth, our method improves stripe-factor estimation accuracy and reduces error in corrected counts relative to bin2cell and bin2cell-derived baselines. Across four public VisiumHD slides, it consistently lowers striping intensity while substantially better preserving biological signal present in the large-scale global count structure and avoiding the artifacts introduced by other methods. AVAILABILITY AND IMPLEMENTATION: All source code and links to publicly available data used for this study are available at https://github.com/paolamalsot/destriping-GLM.

Artifacts↗
PubMed1992

Current concepts in embryonic craniofacial development.

Embryology mirrors phylogeny. The phenotypic expression of the genome is the result of differential gene transcription, the critically timed turning on and off of specific genes by transcription factors to produce cyto-, histo-, and morpho-differentiation that fleetingly reflects evolutionary stages of development during ontogeny. Hox genes regulate transcription of other structural genes and are responsible for patterning of the facial primordia. Cephalic development involves extremely complex morphogenetic mechanisms built on conserved elements that have undergone enormous evolutionary changes. Transient expression of phylogenetic origins characterize ontogeny and are reflected in defective development that may be due to inappropriate expression of Hox genes or distorted or disrupted epignetic processes. The mechanisms by which genetic information is transformed into morphological patterning by the actions of growth factors, morphogenes, and receptors are currently being identified. Biochemical, immunological, and allometric analyses of embryos and fetuses in experimental and descriptive studies are elucidating details of units of craniofacial morphogenesis--faciogenesis, palatogenesis, gnathogenesis, odontogenesis. Three-dimensional model computer-assisted reconstruction of sectioned embryos and fetuses provides a further technique for understanding the complex configurations of tissue migratory patterns and growth sites that account for normal and abnormal craniofaciogenesis.

Animals↗
PubMed1977

[Universal measurement site for the processing-oriented recording of cardiovascular data].

A measuring place is described for the registration of standardized, evaluable by means of the computer deviations of bioelectric signals (parameters of heart and circulation, peripheral pulse curves and rheogramms). The high demands which concern the adequate establishment measuring places with regard to quality and comfort of attendance and condition corresponding technical solutions are explained. At the instance of the rheogram the mode of function is described. A short prognosis on the trend of development in the recognition of biological measuring values is given.

Cardiovascular Diseases↗
PubMed1992

Quantitation and mapping of integrated human papillomavirus on human metaphase chromosomes using a fluorescence microscope imaging system.

Integrated human papillomavirus type 16 (HPV-16) DNA was directly visualized on metaphase chromosomes in the two human cervical carcinoma cell lines SiHa and CaSki by fluorescence in situ hybridization with a biotinylated DNA probe (7.9 kb). The fluorescence intensities of hybridization signals from single copies and dispersed clusters of integrated HPV-16 DNA were quantified using a microscope equipped with a cooled-CCD camera that was interfaced to an image processor and host computer. Hybridization signals were localized on chromosomes using separate, registered images of 4',6-diamidino-2-phenylindole (DAPI) or propidium iodide stained metaphase chromosome spreads. In both SiHa and CaSki spreads, a single fluorescein signal was observed on one or both chromatids of chromosome 13, which was identified by simultaneous hybridization with a biotinylated centromere probe specific for chromosomes 13 and 21. Ratios of the distance from 13pter to the HPV-16 signals to the entire chromosome length were approximately 0.63 +/- 0.05 in both SiHa and CaSki cells, indicating the possibility of a common integration domain on chromosome 13. In SiHa cells, no additional signals were observed on other chromosomes. This observation, taken together with literature reports that SiHa cells contain 1 to 2 copies of the HPV-16 genome in this region of chromosome 13, suggests that each fluorescein signal on chromosome 13 represents one equivalent of the HPV-16 genome. The total integrated fluorescence intensity in isolated CaSki metaphase chromosome spreads was approximately two orders of magnitude greater than that of a single copy of HPV-16 DNA in SiHa cells, indicating an increase in HPV-16 copy number.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

MR imaging of cerebral perfusion by phase-angle reconstruction of bolus paramagnetic-induced frequency shifts.

Phase-angle images are acquired dynamically during bolus paramagnetic contrast injection and demonstrate a phase-enhancement effect in perfused cerebral tissues. Signal-to-noise is comparable to that of susceptibility-based signal loss (delta R*) images. Assuming that phase shift is proportional to the tissue paramagnetic agent concentration, as supported by experimental data, the integrated area of the phase time response curves estimated the relative gray to white matter blood volume as 1.8:1 and was sensitive to acute ischemia. The relation between tissue phase shift and concentration is considered.

Animals↗
PubMedDate not supplied

Noninvasive external recording of cardiac conduction system (His bundle) activity.

Successful and adequate external recording of the cardiac conduction system from the body's surface can be accomplished in 80 to 90 percent of subjects studied. High-gain amplification, signal averaging, and triggering with a conditioned QRS signal results in good recording reproducibility. Averaging of 128 consecutive cycles is adequate, but on occasion averaging of 256 cycles may yield better results. The patients's QRS signal triggers the transfer of signals, which are digitized and stored during the preceding P-R interval. Comparison of external recordings with direct invasive recordings in animals and patients shows good correlation between the major His bundle deflections. The advantages of the system developed include its mobility, triggering the QRS with pretrigger data processing, and instantaneous display on Polaroid photograph. Future research should concentrate on further miniaturization and simplification of the instrumentation, detailed experimental comparison between direct and external recordings for identification of deflections and their origin, further study of the recording lead system, and the most appropriate method of information display.

Animals↗
PubMed1992

Focal liver lesions: MR imaging with Mn-DPDP--initial clinical results in 40 patients.

Manganese (II) N,N'-dipyridoxylethylenediamine-N,N'-diacetate-5,5'-bis(phosphate) (DPDP) was evaluated as a contrast agent for magnetic resonance (MR) imaging (1.5 T) of focal liver lesions in 40 patients. Doses of 5 and 10 mumol/kg were administered intravenously. Mn-DPDP-enhanced T1-weighted images were compared quantitatively and subjectively with standard T1- and T2-weighted nonenhanced images. Use of Mn-DPDP resulted in a statistically significant increase in signal intensity of liver parenchyma in T1-weighted images at both doses. No enhancement was seen in metastases, cholangiocarcinomas, or lymphomas, while all hepatocellular carcinomas were enhanced. Enhancement was seen in focal nodular hyperplasia and in regenerative nodules. The lesion-to-liver contrast in Mn-DPDP-enhanced gradient-recalled-echo images was superior to that of all precontrast images (P less than .01). The number of nonenhancing malignant liver lesions detected in spin-echo (SE) images was increased (272 in T2-weighted SE images vs 390 in T1-weighted Mn-DPDP-enhanced SE images). Image interpretation (eg, visualization and demarcation of the lesions) was markedly better in Mn-DPDP-enhanced images than in all precontrast images (P less than .001).

Adult↗
PubMed1992

Poly(A) RNA codistribution with microfilaments: evaluation by in situ hybridization and quantitative digital imaging microscopy.

The distribution of poly(A) RNA has been visualized in single cells using high-resolution fluorescent in situ hybridization. Digital imaging microscopy was used to quantitate the signal in various cellular compartments. Most of the poly(A) signal remained associated with the cellular filament systems after solubilization of membranes with Triton, dissociation of ribosomes with puromycin, and digestion of non-poly(A) RNA with ribonuclease A and T1. The actin filaments were shown to be the predominant cellular structural elements associating with the poly(A) because low doses of cytochalasin released about two-thirds of the poly(A). An approach to assess the extent of colocalization of two images was devised using in situ hybridization to poly(A) in combination with probes for ribosomes, membranes, or F-actin. Digital imaging microscopy showed that most poly(A) spatially distributes most significantly with ribosomes, slightly less with F-actin, and least of all with membranes. The results suggest a mechanism for anchoring (and perhaps moving) much of the cellular mRNA utilizing the interaction between actin filaments and poly(A).

Actin Cytoskeleton↗
PubMed1977

The role of the digital computer in pediatric cardiology.

A digital computer system is described which allows the real-time processing of all physiological signals obtained during a heart catheterization procedure and which makes all relevant results and informations available immediately during the investigation. In addition, special electronic units and programs have been developed in our institution for the automated extraction of morphological criteria from biplane angiocardiograms. Thereby right and left ventricular volume, shape and contraction pattern can be quantitated and used to characterize the performance of the heart as muscle and pump in physical terms. Recently, complete digital processing of videoangiocardiograms has been achieved in a stroboscopic mode, each videofield in real time. Application of image enhancement, subtraction, integration and restoration techniques leads to a fundamentally improved angiocardiographic image quality for a given amount of injected contrast material. Based on eight years of experience with digital computer application in pediatric cardiology, computer technologies are considered likely to become the method of choice in the future.

Angiocardiography↗
PubMed1975

Quantitative colour-ultrasonography by means of a computer aided simultaneous tomogram.

In this newly developed method, the ultrasonic diagnosis has become quantitative. The data will remain quantitative so far as an image storage tube is used. With the conventional storage type CRT, it is impossible to memorize the reflected echo signals of different strength levels. But with our method, it becomes possible to memorize the images according to individual levels. By the direct digitalization of the ultrasonic echo images, more information is obtained from the reflected echo signals. By processing the original information with a computer, more accurate diagnosis is possible. It is hoped and believed, that this computer aided ultrasonic examination, with single scan display in colour or black and white, will further promote ultrasonic diagnosis in future.

Color↗