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At least 379 records · Page 21Linked to original sources
PubMed1991

Hematopoietic growth factors: interactions and regulation of production.

Hematopoietic growth factors are the major regulatory molecules supporting constitutive and inducible hematopoiesis. Molecular biology techniques have led to the identification and cloning of a series of hematopoietic growth factor genes, and the synthesis of large amounts of these molecules has facilitated investigations or their physiological functions and the network of their interactions. The present article focuses on the role of hematopoietic growth factors, growth-factor-synergizing factors, and growth-factor-releasing factors in the regulation of proliferation, differentiation, and functional activation of hematopoietic stem cells and lineage-committed progenitor cells. Cellular sources of growth factors, signal transduction pathways involved in their gene activation and transcriptional and posttranscriptional mechanisms that govern regulation of expression of these genes are also detailed.

Animals↗
PubMed2005

Transforming growth factor-beta1 and disorders of the lung.

The transforming growth factor (TGF) superfamily encompasses about 30 members in mammals. The effect of TGF-beta subfamily members is exerted and regulated via selective pathways of synthesis and signaling that involve activation of latent TGF-beta, specific and high-affinity binding to cell membrane serine/threonine kinase receptors, activation of intracellular cascades that include Smad molecules and mitogen-activated protein kinases, and regulated termination of the effect by diverse mechanisms including protein degradation and transcriptional activation. Several comprehensive reviews on TGF-beta biology in general and on the role of this cytokine in other diseases have been published recently. In recent years an unexpected role of TGF-beta on lung homeostasis has been revealed. Here, we discuss the contribution of TGF-beta to the pathogenesis of asthma and chronic obstructive pulmonary disease, two common illnesses of the lung, as well as of lymphangioleiomyomatosis, a rare disease in women. The information we collate and integrate places TGF-beta at a pivotal point within complex networks that control lung physiology as well as the physiopathology of these lung diseases.

Animals↗
PubMed2005

Signaling through receptors and scaffolds: independent interactions reduce combinatorial complexity.

After activation, many receptors and their adaptor proteins act as scaffolds displaying numerous docking sites and engaging multiple targets. The consequent assemblage of a variety of protein complexes results in a combinatorial increase in the number of feasible molecular species presenting different states of a receptor-scaffold signaling module. Tens of thousands of such microstates emerge even for the initial signal propagation events, greatly impeding a quantitative analysis of networks. Here, we demonstrate that the assumption of independence of molecular events occurring at distinct sites enables us to approximate a mechanistic picture of all possible microstates by a macrodescription of states of separate domains, i.e., macrostates that correspond to experimentally verifiable variables. This analysis dissects a highly branched network into interacting pathways originated by protein complexes assembled on different sites of receptors and scaffolds. We specify when the temporal dynamics of any given microstate can be expressed using the product of the relative concentrations of individual sites. The methods presented here are equally applicable to deterministic and stochastic calculations of the temporal dynamics. Our domain-oriented approach drastically reduces the number of states, processes, and kinetic parameters to be considered for quantification of complex signaling networks that propagate distinct physiological responses.

Binding Sites↗
PubMed2000

Biochemistry of HER2 oncogenesis in breast cancer.

HER2/ErbB-2 belongs to a family of four receptors that bind growth factors as dimers and transmit cellular signals. The ErbB-2 signaling unit shares functional characteristics with other modules whose function is essential for morphogenesis of epithelial organs, including the mammary gland. However, unlike other receptors, ErbB-2 binds no known growth factor ligand with high affinity, and its oncogenic potential is exceptionally high. Biochemical and genetic lines of evidence imply that ErbB-2 is a unique receptor: by serving as a preferred heterodimeric partner of the other ErbB receptors, it enhances and prolongs cell-to-cell signals. ErbB-2-containing heterodimers are long-lived and their signals are relatively potent because the rate of ligand dissociation is decelerated by ErbB-2, and their rate of endocytosis is relatively slow. Apparently, all ErbB ligands are bivalent molecules, whose low affinity site prefers ErbB-2. Hence, overexpression of ErbB-2 in epithelial tumor cells biases formation of heterodimers, leading to enhanced responsiveness to stromal growth factors and, eventually, to oncogenic transformation. Consequently, removal of ErbB-2 from the cell surface or inhibition of its intrinsic enzymatic activity may reduce oncogenicity. Indeed, anti-ErbB-2 antibodies that can effectively internalize the oncoprotein are therapeutically beneficial. We conclude that ErbB-2 developed as a master regulator of a signaling network essential for normal physiology. However, ErbB-2 opportunistically is exploited by oncogenic mechanisms. This understanding may prove useful for developing clinical strategies to inhibit ErbB-mediated cancer.

Journal Article↗
PubMed2000

Event discovery in medical time-series data.

Vast amounts of clinical information are generated daily on patients in the health care setting. Increasingly, this information is collected and stored for its potential utility in advancing health care. Knowledge-based systems, for example, might be able to apply rules to the collected data to determine whether a patient has a certain condition. Often, however, the underlying knowledge needed to write such rules is not well understood. How could these clinical data be useful then? Use of machine learning is one answer. We present a pipeline for discovering the knowledge needed for event detection in medical time-series data. We demonstrate how this process can be applied in the development of intelligent patient monitoring for the intensive care unit (ICU). Specifically, we develop a system for detecting Otrue alarmO situations in the ICU, where currently as many as 86% of bedside monitor alarms are false.

Artificial Intelligence↗
PubMed2002

Transcriptome analysis and related databases of Lactococcus lactis.

Several complete genome sequences of Lactococcus lactis and their annotations will become available in the near future, next to the already published genome sequence of L. lactis ssp. lactis IL 1403. This will allow intraspecies comparative genomics studies as well as functional genomics studies aimed at a better understanding of physiological processes and regulatory networks operating in lactococci. This paper describes the initial set-up of a DNA-microarray facility in our group, to enable transcriptome analysis of various Gram-positive bacteria, including a ssp. lactis and a ssp. cremoris strain of Lactococcus lactis. Moreover a global description will be given of the hardware and software requirements for such a set-up, highlighting the crucial integration of relevant bioinformatics tools and methods. This includes the development of MolGenIS, an information system for transcriptome data storage and retrieval, and LactococCye, a metabolic pathway/genome database of Lactococcus lactis.

Databases, Nucleic Acid↗
PubMed1992

Immune-neuroendocrine circuits: integrative role of cytokines.

Several efficient autoregulatory mechanisms confer a certain degree of autonomy to the immune system. However, increasing evidence shows that immune processes operate in a coordinated fashion with other body systems. In this article, we discuss concepts and facts concerning interactions between immune and neuroendocrine mechanisms. There are clear examples that immune cells can be influenced by hormones, neurotransmitters, and neuropeptides and also by alterations in brain functions. Conversely, immune-derived products such as lymphokines and monokines can affect endocrine, autonomic, and central mechanisms. Neuroendocrine responses occur during the activation of the immune system. These responses can be elicited by innocuous antigens; they can also be detected during pathological conditions involving immune activation, and in many cases are dissociable from the effects of the disease itself and from the stress of being sick. On this basis, we emphasize the multidirectional nature of the communication processes between the immune, endocrine, and nervous systems. The role of lymphokines and monokines as messengers able to convey information to neuro and endocrine structures about the present state of activity of the immune system is stressed. The relevance of immune-neuroendocrine interactions for immunoregulation and host defenses is discussed as well as the active role of the immune system in mediating metabolic and homeostatic adjustments or derangements during the course of certain infectious, inflammatory, and neoplastic processes. The evidence available suggests that complex immune-neuroendocrine networks operate under both physiological and pathological conditions.

Animals↗
PubMedDate not supplied

[A monitor of the biomechanical cardiac activity].

A monitor of the biomechanical cardiac activity is described, which was elaborated on the basis of the accelerometer sensor and sigma-delta ADC for the purpose of registering the ballistocardiograms and seismocardiograms. The device ensures a non-stop signal recording for as long as 8 hours with the data being preserved in an inbuilt memory. Data are fed to the computer through the USB port. An algorithm is suggested for recordings processing by using the neuron-net technologies.

Algorithms↗
PubMed1990

[A spectral analysis and mathematical modelling of the brain electrical activity in normal rats and in genetically conditioned convulsibility].

Spectral signs of genetically conditioned convulsibility of rats of the Krushinskiĭ-Molodkina (KM) strain were determined when studying the background electrical brain activity. These signs were: an increase of the delta-activity power in motor and visual cortical zones; considerable increase of the hippocampal potential power; weakening of the caudate nucleus potential power. Spectra of biopotentials being approximated by theoretical spectral function, model parameters simulating physiological characteristics of neural networks were estimated (an inverse problem of modelling). Spectral signs of convulsibility were shown to reflect changes in properties of the neural network. On the basis of calculations it is supposed that genetically determined convulsibility of KM rats results from weakening of inhibitory functions of the caudate nucleus as well as from increased excitability (reactivity) of hippocampal and neocortical neurons.

Acoustic Stimulation↗
PubMed1989

[Pathogenesis of transparency disorders of the optical environment of the eye. IV. Electron microscopy study of the vitreous body in chalcosis].

The authors proved, based on electron microscopic analysis that the vitreous body of the rabbit creates under physiological conditions a regular network of collagenous fibrils with a different cell population. The cells can be divided into three basic types: 1. Large cells with a lobular nucleus and well differentiated cytoplasm and multiple organelles which ensure a high metabolic activity. 2. The second type are cells of an elongated shape with an oval nucleus surrounded by a thin layer of cytoplasm with a small amount of organelles. 3. The third type are large globular cells with a homogeneous structureless mass. The basic cytoplasm with the nucleus and a negligible amount of organelles is pushed to the cell surface and thus forms a thin layer beneath the plasmalemma. Contrary to the pathologically altered vitreous body, the authors did not detect on the sound vitreous body any phagocytosing cells. On the other hand, the long-term effect of copper in experimental chalcosis markedly alters the cytological character of the structure of the vitreous body. Cell types typical for a sound vitreous body were not found in the affected eye in chalcosis. In addition to rare destroyed cells containing autophagosomes of varying size with incomplete plasmalemma at some sites there is the important finding of two different forms of phagocytes in the pathological vitreous body: 1. Neutrophil granulocytes and 2. Macrophages containing large phagosomes in the cytoplasm. Their function is to eliminate destroyed tissues and engulfing of copper particles.

Animals↗
PubMed1978

[Cytological recognition of the histological types of lymphogranulomatosis in children].

Examinations of punctates and impressions of lymph nodes from 68 children with primary untreated lymphogranulomatosis permitted to develop the criteria for differential cytological diagnosis of all types and variants of lymphogranulomatosis on the basis of histogenetic analysis and clinico-morphological comparisons, according to histological classification of the WHO. This proved to be possible only after it had been assumed that the original tumor cell must be a semi-stem cell of bone-marrow origin of histiocytic-reticular shoot which normally provides for physiological regeneration of reticular network of the lymph node. It appears that such a cell is a small lymphocyte-like cell with invaginated nucleus, the so-called small cleaved cell.

Child↗
PubMed1994

Advanced clinical monitoring: considerations for real-time hemodynamic diagnostics.

In an effort to ease staffing burdens and potentially improve patient outcome in an intensive care unit (ICU) environment, we are developing a real-time system to accurately and efficiently diagnose cardiopulmonary emergencies. The system is being designed to utilize all relevant routinely-monitored physiological data in order to automatically diagnose potentially fatal events. The initial stage of this project involved formulating the overall system design and appropriate methods for real-time data acquisition, data storage, data trending, waveform analysis, and implementing diagnostic rules. Initially, we defined a conceptual analysis of the minimum physiologic data set, and the monitoring time-frames (trends) which would be required to diagnose cardiopulmonary emergencies. Following that analysis, we used a fuzzy logic diagnostic engine to analyze physiological data during a simulated arrhythmic cardiac arrest (ACA) in order to assess the validity of our diagnostic methodology. We used rate, trend, and morphologic data extracted from the following signals: expired CO2 time-concentration curve (capnogram), electrocardiogram, and arterial blood pressure. The system performed well: The fuzzy logic engine effectively diagnosed the likelihood of ACA from the subtle hemodynamic trends which preceded the complete arrest. As the clinical picture worsened, the fuzzy logic-based system accurately indicated the change in patient condition. Termination of the simulated arrest was rapidly detected by the diagnostic engine. In view of the effectiveness of this fuzzy logic implementation, we plan to develop additional fuzzy logic modules to diagnose other cardiopulmonary emergencies.

Algorithms↗
PubMed1995

[Systematization in the Central Clinical Laboratory of Kyoto University Hospital].

Recently, computer systems including several delivery systems have been installed in the Central Clinical Laboratory of Kyoto University Hospital. As for the physiological examination system, we have introduced PRINS (Physiological-examination Result Information Network System) using an NEC computer and LAN. Utilizing Windows, this PRINS is connected to individual systems and equipment, and the data are sent to the host computer system (KING: Kyoto University Hospital Information Network Galaxy, which utilizes IBM). This system enabled us to greatly improve (1) the efficacy of examinations, (2) management and data-stock of huge volumes, (3) rapid data analyses and simplicity in handling, and (4) facility of reception and reservation business. As for the sample analysis system, we formerly developed computer systems using MUMPS independently in the subdivisions. At the time of delivery system installation, we decided to unify them and newly establish a general managing system using MUMPS Sumitomo Electric Industries. The purpose of these installations are briefly as follows; (1) to reduce human power and to simplify delivery of samples and related business, (2) to report the assay results rapidly, (3) to improve and automate the quality controls, (4) to prevent from infections, and (5) to make handling and work easier. This system is comprised of biochemistry, immunology, hematology and emergency examination subdivisions, and connects each part in a network system using LAN. This is further connected to KING, the host. Actually, 4 sample delivery lines from 3 industries were introduced: Hitachi for biochemistry, Sysmex for hematology, and Toshiba-IDS for coagulation and immunology. Monitoring and data analyses including quality controls are performed by a host system or individual systems (biochemistry and hematology). At present, such heterogeneous installations were considered to be most suitable for our purpose and these made it possible to continue assays of other lines even when trouble occurred in one of the lines. In addition to the general systems, we have introduced various software programs for statistical analyses. These have been effectively utilized already for detailed setting of the clinical reference values for hematology data, and also for a computer diagnosis trial for anemia related diseases. When effective operations of these newly installed systems is achieved, we would like to extend our efforts to establish an ideal laboratory which is able to assist the intensive medi-care system in the university hospital.

Clinical Laboratory Information Systems↗
PubMed1997

Considerations for developing a clinical capnogram monitoring system.

Clinical monitoring and diagnostic systems may require the analysis of multiple physiologic signals to generate a diagnosis. The complexity of these systems is formidable for at least two reasons: clinical physiologic signals are noisy, and systems built around multiple signals may fail when any single signal is absent. In view of these limitations, we have been developing a clinical respiratory CO2 waveform (capnogram) diagnostic system. The purpose of this system is to develop a differential diagnosis from a single signal for subsequent evaluation within the context of multiple single-signals. This paper will review the development issues which we have been confronting, and discuss the tools and methods which have been successful.

Adult↗
PubMed2005

Dynamic neural network models of the premotoneuronal circuitry controlling wrist movements in primates.

Dynamic recurrent neural networks were derived to simulate neuronal populations generating bidirectional wrist movements in the monkey. The models incorporate anatomical connections of cortical and rubral neurons, muscle afferents, segmental interneurons and motoneurons; they also incorporate the response profiles of four populations of neurons observed in behaving monkeys. The networks were derived by gradient descent algorithms to generate the eight characteristic patterns of motor unit activations observed during alternating flexion-extension wrist movements. The resulting model generated the appropriate input-output transforms and developed connection strengths resembling those in physiological pathways. We found that this network could be further trained to simulate additional tasks, such as experimentally observed reflex responses to limb perturbations that stretched or shortened the active muscles, and scaling of response amplitudes in proportion to inputs. In the final comprehensive network, motor units are driven by the combined activity of cortical, rubral, spinal and afferent units during step tracking and perturbations. The model displayed many emergent properties corresponding to physiological characteristics. The resulting neural network provides a working model of premotoneuronal circuitry and elucidates the neural mechanisms controlling motoneuron activity. It also predicts several features to be experimentally tested, for example the consequences of eliminating inhibitory connections in cortex and red nucleus. It also reveals that co-contraction can be achieved by simultaneous activation of the flexor and extensor circuits without invoking features specific to co-contraction.

Animals↗