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[Functional late results following peripheral replantation].

To obtain comparable ratings of late results after replantations a plan of examination is presented, including sensibility, function of tendons, degree of decrease in total hand function, integration of the replanted finger into hand function, subjective judgement of the result by the injured person, and persistent pain. Examination of 84 finger replantations showed the following results: 20% very good, 45% good, 27% satisfactory, and 10% poor.

Amputation, Traumatic↗

Integration of postprandial function in the proximal gastrointestinal tract. Role of CCK and sensory pathways.

Cholecystokinin (CCK) stimulates vagal afferent fiber discharge, both gastric and intestinal, which seems to result in reflex decrease in gastric motility, gastric acid secretion, and stimulation of pancreatic protein secretion. Endogenous release of CCK by fat or soybean trypsin inhibitor also alters function by way of a capsaicin-sensitive pathway. We suggest that CCK is released locally from the intestine and acts locally or systemically to stimulate vagal afferent fiber discharge to alter proximal gastrointestinal function (Fig. 14). In this way, in addition to its effect on food intake, CCK and the neural pathway integrate function in the proximal gastrointestinal tract, regulating the entry of food into the duodenum to ensure effective digestion and absorption.

Afferent Pathways↗

Modeling total heart function.

Computational models of the electrical and mechanical function of the heart are reviewed. These models attempt to explain the integrated function of the heart in terms of ventricular anatomy, the structure and material properties of myocardial tissue, the membrane ion channels, and calcium handling and myofilament mechanics of cardiac myocytes. The models have established the computational framework for linking the structure and function of cardiac cells and tissue to the integrated behavior of the intact heart, but many more aspects of physiological function, including metabolic and signal transduction pathways, need to be included before significant progress can be made in understanding many disease processes.

Animals↗

Valva ileocaecalis: preservation during ileocolonic surgery employing a rodent experimental model.

Experimental and clinical data suggest that the valva ileocaecalis under neurogenic and hormonal influences, modulates antegrade and retrograde flow of succus entericus. A priori reasoning suggests that this function may influence nutrient absorption by and intraluminal endogenous microbial flora within the ileum. The hypothesis to be tested was, can anatomical and functional integrity of the valva ileocaecalis be preserved during the performance of a right hemicolectomy with reestablishment of intestinal continuity via a cecocolostomy? The methodology involved utilization of Lewis male rats weighing approximately 500 gm. General anesthesia was induced for all procedures. The animals were randomly assigned to three groups (10 animals/group): (A) sham operation; (B) pericecal dissection (preservation of the arteria et vena ileocolica); and (C) periileal dissection (ligation of the aforementioned vessels). Celiotomy was performed employing standard clean techniques, and was accompanied by a right hemicolectomy and an end-to-end or end-to-side cecocolostomy. Function of the heterotopic valva ileocaecalis was assessed 6-12 weeks post-operatively employing radiographic criteria (fluoroscopic analysis after intraluminal instillation of barium sulfate). Light microscopic analysis was performed subsequent to the radiographic studies. Periileal dissection associated with ligation of the arteria et vena ileocolica uniformly resulted in anastomotic disruption. Pericecal dissection associated with preservation of those vessels resulted in uniform anastomotic integrity, although two animals succumbed secondary to pneumonitis within 5 post-operative days. Radiographic analysis of the heterotopic valva ileocaecalis revealed intermittent antegrade and no retrograde flow of contrast material, which suggested functional integrity. Qualitative light microscopic analysis revealed architectural integrity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Inorganic lead exposure in battery and paint factory: effect on human sperm structure and functional activity.

Lead is one of the industrially important heavy metals that causes male reproductive impairment among battery and paint factory workers, but information on the structure-function integrity of human spermatozoa is still limited. Therefore, it was necessary to investigate the effect of lead on sperm structure and functional activity in these workers. Oligozoospermia with concomitant lowering of sperm protein and nucleic acid content and the percentage of sperm DNA hyploidy (P <0.001) suggested the diminution of sperm cell production after occupational lead exposure. Low sperm vitality and hypoosmotic swelling percentage along with high malondialdehyde content and altered seminal plasma ascorbate level (P<0.001) indicating damage of sperm cell surface, might be due to high membrane lipid peroxidation and failure of non-enzymatic antioxidant protection after lead exposure. Alteration of sperm membrane surface was also evidenced from scanning electron microscopy and further authenticated by atomic and lateral force microscopy. Lowering of sperm velocity, gross and forward progressive motility with high stationary motile spermatozoa (P<0.001) suggested retarded sperm activity among the exposed workers, which was supported by high seminal plasma fructose level and reduced activity of sperm ATPase (P < 0.001). Increased incidence of teratozoospermia was also associated with high blood and semen lead level (PbB, PbS) (P<0.001). Therefore, the results suggested that lead not only affects the sperm count, but also damages the sperm structure and membrane integrity, motility and functional activity among the battery and paint factory workers.

Chemical Industry↗

Functionally and structurally integrated computational modeling of ventricular physiology.

Computational biology is integrative in several ways. Functionally, computational models are valuable for integrating the many interacting processes within biochemical networks and the many interacting physiological subsystems within the cell. Structurally detailed models provide a way of integrating across scales of biological organization from molecule to organism. Data integration across diverse laboratory and clinical measurements is another unique strength of computational biology. We describe examples of all three categories of integration by using recent advances in modeling cardiac excitation-contraction coupling and whole-heart electromechanics in health and disease.

Animals↗

Role of glutathione redox cycle and catalase in defense against oxidative stress induced by endosulfan in adrenocortical cells of rainbow trout (Oncorhynchus mykiss).

The role of antioxidants in maintaining the functional integrity of adrenocortical cells during in vitro exposure to endosulfan, an organochlorine pesticide, was investigated in rainbow trout (Oncorhynchus mykiss). Aminotriazole (ATA), an inhibitor of catalase (CAT), L-buthionine sulfoximine (L-BSO), an inhibitor of glutathione (GSH) synthesis, and N-acetyl cysteine (NAC), a glutathione precursor, were used to investigate the role of CAT and GSH redox cycle in protection against the adrenal toxicity of endosulfan, a pesticide that impairs cell viability (LC50 366 microM) and cortisol secretion (EC50 19 microM) in a concentration-related manner. Pretreatment with ATA and L-BSO enhanced the toxicity of endosulfan (LC50 and EC50, respectively, 302 and 2.6 microM with ATA, 346 and 3.1 microM with L-BSO), while pretreatment with NAC had no significant effect on cell viability and increased the EC50 of endosulfan to 51 microM. CAT activity was significantly reduced following exposure to endosulfan when cells were pretreated with ATA. Pretreatment with L-BSO significantly decreased glutathione peroxidase (GPx) activity and reduced glutathione (GSH) levels in a concentration-related manner following exposure to endosulfan, while GSH levels were significantly higher in NAC pretreated cells compared to untreated cells. Finally, pretreatment with ATA and L-BSO increased, while pretreatment with NAC decreased, lipid hydroperoxides (LOOH) levels. CAT, GPx, and GSH were identified as important antioxidants in maintaining the function and integrity of rainbow trout adrenocortical cells and ATA, L-BSO, and NAC were identified as effective modulators of CAT and GSH redox cycle. Moreover, this study suggests that the glutathione redox cycle may be more efficient than catalase in protecting adrenocortical cells against endosulfan-induced oxidative stress.

Acetylcysteine↗

Cerebral monitoring in the operating room and the intensive care unit - an introductory for the clinician and a guide for the novice wanting to open a window to the brain. Part II: Sensory-evoked potentials (SSEP, AEP, VEP).

An evoked potential differs from the EEG mainly in two ways: 1. The EEG is a random, continuous signal, which arises from the ongoing activity of the outer layers of the cortex. An evoked potential is the brain's response to a repetitive stimulus along a specific nerve pathway. 2.EEG signals range from 10-200 milliVolt (mV). Evoked potentials are smaller in amplitude (1-5-20 microVolt requiring precise electrode positioning and special techniques (signal averaging) to extract the specific response from the underlying EEG "noise". The technique of signal averaging, as originally described by Dawson in 1954 [69J, has been further developed in computer processing. The technique is now used by applying a stimulus repeatedly--preferably at randomized intervals--and to record the evoked response over the corresponding area of the brain, averaging out mathematically the change over the number of stimuli. Rationale for the use of EPs in the OR and the ICU. Evoked potentials (EPs) serve the following major purposes: 1. Monitoring of the functional integrity of neural structures that may be at risk during, for instance, ECC (extracorporeal circulation) or endarterectomy indicating cerebral hypoxia. 2. Monitoring of the effects of anesthetic agents and other centrally active drugs, which, besides the cortex, affect deeper neuronal structures. 3. Orthopedic cases where the spinal cord is at risk such as Harrington rod insertion and removal. 4. Clamping of the abdominal aortic artery during aneurysmectomy resulting in a potential damage of the lower parts of the spinal cord. 5. Clipping of an intracerebral aneurysm, which may be impeding blood flow to vital cerebral textures. 6. An indicator of cerebral hypoxia when the blood pressure is deliberately lowered. 7. Operation on peripheral nerves and nerve roots to identify early trauma. 8. Monitoring the cerebral function during controlled hypothermia when the EEG becomes flat. 9. Monitoring of the pathophysiological conditions after severe head trauma and the effects of therapy. 10. An intraoperative warning device of unsuspected awareness during light anesthesia when movement is abolished by muscle relaxants and cardiovascular responses are modified by vasoactive drugs. In case of the latter the stimulus is a small electrical potential applied to the skin of the hand. Thereafter, the stimulus travels along the specific nervous pathways inducing (= generating) potential activation at various sites. The generation of potential changes at various sites along the pathway is an index for the integrity of the nerve. Thus, the evoked potential can be considered a neurophysiological response (usually of the cortex) to impulses originating from some externally stimulated sensory nerve. They provide a physiological measure of the functional integrity of the sensory nerve pathway, which can be used as a clinical diagnostic tool as well as for intraoperative monitoring. The evoked potential usually is recorded from the specific cortical area corresponding to the stimulus input. The classification of evoked potentials. Stimulating a sensory nervous pathway induces evoked potentials. If the auditory nerve is stimulated by "clicks" from headphones, it is called the auditory evoked potential (AEP). The early part of the AEP waveform (less than 10 msec) is called the Brainstem Auditory Evoked Potential (BAEP) since it reflects the passing of the impulse through the brainstem. If a nerve on the arm or the leg is stimulated by a small electrical current applied to the overlying skin, it is called the Somatosensory Evoked Potential (SSEP). If, however, the retina is stimulated by means of flicker light or a sudden change in a checkerboard pattern, the evoked potential thus recorded over the corresponding cortical area is called the Visual Evoked Potential (VEP). Evoked potentials are used both as a diagnostic tool and as a monitoring technique. As diagnostic tests, evoked potentials are useful to evaluate neurologic disorders such as: a) multiple sclerosis, b) acoustic nerve tumors, and c) optic neuritis. As a monitoring modality, evoked potentials are used during all surgical procedures, which might compromise part of the brain or the spinal cord.

Brain↗

Model for a robust neural integrator.

Integrator circuits in the brain show persistent firing that reflects the sum of previous excitatory and inhibitory inputs from external sources. Integrator circuits have been implicated in parametric working memory, decision making and motor control. Previous work has shown that stable integrator function can be achieved by an excitatory recurrent neural circuit, provided synaptic strengths are tuned with extreme precision (better than 1% accuracy). Here we show that integrator circuits can function without fine tuning if the neuronal units have bistable properties. Two specific mechanisms of bistability are analyzed, one based on local recurrent excitation, and the other on the voltage-dependence of the NMDA (N-methyl-D-aspartate) channel. Neither circuit requires fine tuning to perform robust integration, and the latter actually exploits the variability of neuronal conductances.

Computer Simulation↗

Pathology of intrinsic cardiac neurons from ischemic human hearts.

Various populations of intrinsic cardiac neurons influence regional cardiac function tonically. It is not known whether such neurons are affected by disease states and, if so, in what manner. Therefore, the morphology of intrinsic cardiac ganglia obtained from patients with angiographic evidence of compromised regional coronary blood supply was studied. Posterior atrial ganglia and surrounding fat, removed at the time of cardiac surgery, were placed immediately in saline and within 15-120 min (average of about 40 min) in 0.5% paraformaldehyde/2.5% glutaraldehyde. In 32 studied ganglia, 35% of 473 intrinsic cardiac neurons displayed striking pathological changes at the light and ultrastructural level. The other cells displayed normal morphology. The cytoplasm of 74% of the abnormal cells had one or more of three types of inclusions: (1) darkly stained lamellated inclusions (Type I), (2) membrane-bound whorls and parallel arrays of lightly stained membranes, as well as fine granular material (Type II), or (3) concentric layers of lightly stained membranes with a darker, granular core (Type III). Neurons with inclusions were markedly enlarged (66 x 54 microm vs. 40 x 34 microm for normal neurons) and displayed fewer dendrites. Some neurons contained electron lucent vacuoles indicative of degeneration while others showed frank degeneration, being fragmented, shrunken, and misshapen. Phagocytic cells containing lamellated inclusions and cellular debris were found in ganglia with abnormal neurons. Some axon terminals also displayed degenerative changes. The identification of pathological changes in the human intrinsic cardiac nervous system has implications with respect to the functional integrity of this final common regulator of cardiac function in disease states.

Adult↗

Intraoperative facial nerve monitoring (IFNM) predicts facial nerve outcome after resection of vestibular schwannoma.

Intraoperative facial nerve monitoring (IFNM) is a suitable technique for intraoperative facial nerve identification and dissection, especially in large vestibular schwannomas (VS) (acoustic neuroma). To evaluate its feasibility for estimating functional nerve outcome after VS resection 60 patients underwent surgery using IFNM. Out of this group the last 40 patients were included in a prospective study evaluating the prognostic value of various IFNM parameters (proximal and distal absolute EMG amplitude, stimulation threshold, and proximal-to-distal amplitude ratio) for prediction of initial postoperative facial nerve function and recovery of function. Stimulation threshold and absolute EMG amplitude proximally at the brain stem were both predictive for postoperative nerve function. Good initial facial nerve outcome (modified House Brackmann grading, mHB degree I and degree II) was found in 15/16 patients with a proximal EMG amplitude greater than 800 microV and in 19/22 patients with proximal stimulation threshold less than 0.3 mA. Sixteen of 16 patients with proximal stimulation threshold equal to or greater than 0.3 mA had moderate-to-severe facial palsy (mHB degree III or worse). Six of six patients without evokable proximal amplitude initially had insufficient nerve function (mHB degree IV). Intraoperative decrease of the proximal amplitude was associated with an unfavourable outcome, whereas distal amplitudes usually stayed unchanged. Mean distal EMG amplitudes were also found to be decreased with poor nerve function, which may mean that the tumour had already affected the nerve. A proximal amplitude of 300 microV or less and a proximal-to-distal amplitude ratio below 1:3 were found in the absence of functional recovery in 6/8 (75%) and 5/6 (83%) patients with initial mHB degree IV, respectively. Two patients with initial mHB degree IV improved to mHB degree III despite intraoperative evidence of missing functional nerve integrity. Therefore, functional recovery cannot be predicted by IFNM in all cases of anatomical nerve preservation. We conclude that a minimum follow-up period of 1 year may still be advisable even in certain patients without evidence of intraoperative functional nerve integrity.

Adult↗

Decreased gill ATPase activities in the freshwater fish Channa punctata (Bloch) exposed to a diluted paper mill effluent.

Aquatic habitat is affected by paper mill effluent discharge in many ways. The effect of paper mill effluent on the gill ATPases was studied in freshwater fish Channa punctata (Bloch) exposed to 1%(v/v) of effluent for 15, 30, and 60 days. There was a time-dependent significant (P<0.05-0.001) decrease in all the ATPase activities measured, viz., total, Na(+), K(+)--and ouabain-insensitive ATPase in gill. ATPases play an important role in maintenance of functional integrity of plasma membrane and in several intracellular functions and are considered to be a sensitive indicator of toxicity. In addition to this, branchial ATPases are intimately involved in osmoregulation, acid-base regulation, and respiration of fish. The inhibition of ATPases in gills by, e.g., paper mill effluent could cause disruption of these processes. It is suggested that measurement of ATPases could also be used as a surrogate biomarker of exposure to chemical pollutants.

Animals↗

Semantic integration in healthcare networks.

A seamless support of information flow for increasingly distributed healthcare processes requires to integrate heterogeneous IT systems into a comprehensive distributed information system. Different standards contribute to ease this integration. In a research project focussing on the development of a reference architecture for inter-institutional health information systems, we identified concurring standards currently in use. We therefore categorized these integration standards by distinguishing between technical and semantic integration on the one hand, and data and functional integration on the other hand. In addition, standards for semantic integration are roughly categorized according to their scope. By placing standards into a corresponding matrix a "semantic gap" is revealed, which cannot be covered by standards as it contains volatile medical concepts. As a conclusion, it is recommended to conceptually consider the necessity of system evolution in system architectures and also in future integration standards.

Hospital Information Systems↗

Reduction in BOLD fMRI response to primary visual stimulation following alcohol ingestion.

The physiology of alcohol's effects on brain function is poorly understood. Emission tomographic imaging has revealed both acute and chronic alterations in resting cerebral hemodynamics and metabolism following alcohol ingestion. However, cerebral functional integrity under these conditions has received less attention. Functional magnetic resonance imaging (fMRI) offers a non-invasive method for assessing brain functional activation. In order to assess its utility for studying the effect of alcohol on brain function, we performed fMRI with photic stimulation before and after administration of either 0.7 mg/kg alcohol (N = 12) or placebo (N = 5), resulting in peak breath alcohol levels averaging 0.069 g/dl. We found that the amplitude of visual cortical activation in response to photic stimulation was significantly reduced by approximately 33% following alcohol administration (4.0 +/- 1.7% vs. 2.7 +/- 1.3%, P = 0.02), but not following placebo (4.2 +/- 1.5% vs. 4.1 +/- 1.4%, P = 0.7). The results also suggest that the baseline right hemispheric predominance of activation in response to photic stimulation may be reduced following alcohol, suggesting a greater effect on the right hemisphere, consistent with previous studies and alcohol's known effects on visuospatial processing. In addition, through the course of each activation session, there was a progressive reduction in response following alcohol. These data demonstrate that the cerebral effects of alcohol intoxication can be studied with fMRI, and that the effects on brain function of even moderate alcohol intoxication may be widespread, may be lateralized, and may include the visual system.

Adult↗

An expression analysis of a gene family encoding plasma membrane aquaporins in response to abiotic stresses in Arabidopsis thaliana.

Aquaporin belongs to a highly conserved group of membrane proteins called major intrinsic proteins that facilitate water transport across biological membranes. The genome of Arabidopsis encodes 35 aquaporin genes with 13 homologs in the plasma membrane intrinsic protein (PIP) subgroup. However, the function of each individual aquaporin isoform and the integrated function of plant aquaporins under various physiological conditions remain unclear. As a step toward understanding the aquaporin function in plants under various environmental stimuli, the expressions of a gene family encoding 13 PIPs in Arabidopsis thaliana under various abiotic stress conditions including drought, cold, and high salinity, or abscisic acid (ABA) treatment were investigated by a quantitative real-time reverse transcription-PCR analysis. Several PIP genes were predominantly expressed either in the roots or in the flowers. The expressions of both the highly expressed aquaporins including PIP1;1, PIP1;2, and PIP2;7 and the weakly expressed aquaporins such as PIP1;4, PIP2;1, PIP2;4, and PIP2;5 were modulated by external stimuli. The analyses of our data revealed that only the PIP2;5 was up-regulated by cold treatment, and most of the PIP genes were down-regulated by cold stress. Marked up- or down-regulation in PIP expression was observed by drought stress, whereas PIP genes were less-severely modulated by high salinity. The responsiveness of each aquaporin to ABA were different, implying that the regulation of aquaporin expression involves both ABA-dependent and ABA-independent signaling pathways. Together, our comprehensive expression profile of the 13 members of the PIP gene family provides novel basis to allocate the stress-related biological function to each PIP gene.

Abscisic Acid↗

Functional exploration of the C. elegans genome using DNA microarrays.

Global changes in gene expression underlie developmental processes such as organogenesis, embryogenesis and aging in Caenorhabditis elegans. Recently developed methods allow gene expression profiles to be determined selectively for individual tissues and cell types. Results from both whole-animal and tissue-specific expression profiling have provided an unprecedented view into genome organization and gene function. Integration of these results with other types of functional genomics data gathered from RNA-mediated interference and yeast two-hybrid analyses will allow rapid identification and exploration of the complex functional gene networks that govern C. elegans development.

Animals↗

Zinc-finger transcription factor Gfi-1: versatile regulator of lymphocytes, neutrophils and hematopoietic stem cells.

PURPOSE OF REVIEW: Gfi-1, originally identified as a transcriptional repressor in lymphoid cells, is now recognized to have essential, independent functions in neutrophil maturation and hematopoietic stem cell biology. Here we review recent studies pertaining to Gfi-1 and its cell context specific functions in hematopoietic development. RECENT FINDINGS: Progress in mapping the precise timing of requirements for myeloid transcription factors during hematopoietic development reveals a more refined picture of their sequence of action. We contrast Gfi-1's role in neutrophil development with PU.1, C/EBPalpha, and C/EBPepsilon. Gfi-1 has been found to be a major regulator of adult hematopoietic stem cells. It is required for restricting the proliferation of hematopoietic stem cells and maintaining their functional integrity. We discuss its role and compare its function with that of other regulators recently implicated in the biology of hematopoietic stem cells. SUMMARY: Considerable progress has been made in understanding Gfi-1's context-sensitive roles at defined stages of hematopoietic differentiation.

Animals↗

Site-specific integration of corynephage phi16: construction of an integration vector.

Phi16, a temperate phage induced from Corynebacterium glutamicum ATCC 21792, lysogenizes its host via site-specific recombination. The phage attachment site, attP, was located to a 6.5 kb BamHI fragment of the phi16 genome. This fragment also contained phi16 integrative functions. The minimal phage DNA fragment required for integration was defined. This 1630 bp region contained a large open reading frame, int, encoding a protein of 416 amino acids with similarity in its carboxyl-terminal domain to tyrosine recombinases and particularly to the Xer recombinases. The comparison of the nucleotide sequences of attB, attL, attR, and attP identified a common 29 bp sequence, the core sequence. It lies 11 bp downstream of the 3' end of the integrase gene. phi16 integrase was shown to catalyse site-specific integration in trans to attP with an efficiency of 5x10(3) integrants per microg DNA. The integrating fragment catalysed integration in several Corynebacterium strains that are not infected by phi16, thus enlarging the host spectrum of integrating vectors derived from phi16. In these strains, the phi16 attB site was located in a conserved intergenic region and lies downstream of a clp gene.

Bacterial Proteins↗