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New equipment for a radiation therapy simulator: a device for simplifying irregular field shaping and integrating simulator and therapy machine.

Shaping of irregular treatment fields was facilitated by our newly developed Niwa-Fujikawa irregular field-shaping unit, which was mounted onto a standard radiation therapy simulator. The introduction of a "fieldgraph" led to the functional integration of the simulator and therapy machine. A fieldgraph is a radiograph of an irregular treatment field taken on the Niwa-Fujikawa unit at the same distance as the focus-to-shadow-tray distance of the corresponding therapy machine. The fieldgraph can be taken at the same time as the portal localization film. Through the fieldgraph, which is positioned on the shadow tray of the therapy machine, the irregular treatment field is directly projected onto the skin of the patient. Consequently, marking the irregular field on the skin of the patient is unnecessary. The authors believe that both the new unit and the fieldgraph contribute to greater efficiency and accuracy in daily application of radiation therapy.

Humans↗

Disinhibition as a basic process in the expression of striatal functions. II. The striato-nigral influence on thalamocortical cells of the ventromedial thalamic nucleus.

Besides the nigro-collicular pathway, the nigro-thalamic projection to the ventromedial thalamic nucleus represents another efferent system of the basal ganglia through which striatum can influence motor centers. Since the striato-nigrothalamic circuit is composed of two successive GABAergic inhibitory links and the SNR is tonically active, we tested that by inhibiting nigrothalamic cells, the striatum may exert a facilitatory influence on VM-thalamocortical cells. We show that a transitory block of SNR (substantia nigra pars reticulata) firing (induced by either intranigral application of GABA or by stimulating the inhibitory striato-nigral pathway), causes a perfectly time-locked increase of activity in a large number of VM cells projecting to motor cortex. Moreover, the striatally evoked excitation of VM-thalamocortical cells requires the functional integrity of the GABAergic striato-nigral link. We conclude that the double inhibitory striato-nigrothalamic pathway acts on VM-thalamocortical cells through a disinhibitory mechanism. The functional implication of such a mechanism is discussed.

Animals↗

Delusions: a review and integration.

Delusions are often prominent symptoms in schizophrenia and other psychiatric and neurologic disorders. Despite the central descriptive importance of delusions, there is a paucity of comprehensive reviews, theoretical formulations, and empirical evaluations in this area. Research and theoretical work pertinent to delusions are reviewed with particular emphasis on current findings in the neurobiological, cognitive, and information-processing literature. Research on delusional thought seen in various psychiatric disorders is reviewed and integrated with critical aspects of schizophrenia research. Consideration of three factors may help in understanding delusional thought processes. These factors are state-trait variables, perseverative thought, and cognitive functional integrity.

Delusions↗

Canopy processes research.

The forest canopy regulates the exchange of carbon, water and energy between the ecosystem and the atmosphere, and provides a habitat for a wide variety of species. Understanding canopy processes is important for modeling forest production and carbon sequestration, and for predicting the effects of global changes in climate and atmospheric chemistry on the functioning of forest ecosystems. The Canopy Processes Working Group of the International Union of Forest Research Organizations has provided a forum for researchers working on forest canopies for nearly 20 years, principally through international meetings held every 2-3 years. In this paper, I review the history of the Canopy Processes Group, show how the research focus has changed and broadened, and provide a brief overview of some of the problems that remain to be solved. These include the topic of our 2001 meeting (Linking the Complexity of Forest Canopies to Ecosystem and Landscape Function), integration of canopy and respiratory processes, carbon allocation, physiological changes with tree age, predicting the response of forests to global change, understanding the genetic control of canopy structure and function, and scaling ecophysiological processes and modeling. Determining how forests will respond to global change and understanding the physiology of forest production will require increased attention to canopy processes and an increased focus on the interactions of canopy processes with other components of the ecosystem.

Carbon↗

Colorectal hyperplasia and inflammation in keratin 8-deficient FVB/N mice.

We report that keratin 8 (mK8) gene disruption causes colorectal hyperplasia in FVB/N mice. The intestinal lesions affect uniformly the cecum, colon, and rectum but not the small intestine. The elongation of the crypts is accompanied by an inflammation of the lamina propria and submucosa. Hepatic, renal, and pancreatic functions tested in clinical assays are within nonpathological range, suggesting that the major defect lies in colonic epithelial cells. Still, small but consistent elevation in the hepatic enzymes alanine (AST) and asparate (ALT) aminotransferase are observed, along with a 70% increase in spleen weight. No homozygous mouse line has been established, because of a markedly reduced fertility of the mK8-/- females. Previously, we reported that the mK8- targeted mutation causes embryonic lethality in (C57B1/6x129Sv) mice. This strong effect of the genetic background on the mK8- mutant phenotype emphasizes the importance of using several inbred mouse strains to reveal the polygenic contribution to mutant phenotypes. Our results demonstrate that genetic modifiers of K8/K18 filament functions, with profound effects on embryogenesis and gut functional integrity, are differentially active in the FVB/N and C57B1/6 genetic backgrounds. More importantly, the increase in mK8-/- gut epithelial cell number, rather than cell disruption, contrasts with the known function of epidermal keratins in providing mechanical strength.

Aging↗

Direct biologically based biosensing of dynamic physiological function.

Dynamic regulation of biological systems requires real-time assessment of relevant physiological needs. Biosensors, which transduce biological actions or reactions into signals amenable to processing, are well suited for such monitoring. Typically, in vivo biosensors approximate physiological function via the measurement of surrogate signals. The alternative approach presented here would be to use biologically based biosensors for the direct measurement of physiological activity via functional integration of relevant governing inputs. We show that an implanted excitable-tissue biosensor (excitable cardiac tissue) can be used as a real-time, integrated bioprocessor to analyze the complex inputs regulating a dynamic physiological variable (heart rate). This approach offers the potential for long-term biologically tuned quantification of endogenous physiological function.

Animals↗

Scanning electron microscopic evaluation of variably angled end-to-side microvascular anastomoses.

A comparison of right-angled and opposing oblique-angled end-to-side microvascular anastomoses with both patent and occluded recipient vessels was performed in rats. Patency rates after 3 weeks were comparable in all types of anastomoses (average, 92%). However, scanning electron microscopic evaluation revealed a variety of both nonspecific (pits, craters, folds, etc.) and angle-dependent (mounds, erosions, bridges, etc.) endothelial alterations. It is concluded that, in proximally patent recipient vessels, the functional integrity of the anastomosis is not related to the grafting angle; however, in proximally occluded recipient vessels, retrograde-directed oblique angles may lead to progressive embarrassment of anastomotic function.

Animals↗

[Granulocyte transfusions. Technical data, granulocyte function and results].

A new method called "repetitive filtration leukopheresis" is described for granulocyte transfusion therapy. 23 patients received a total of 91 transfusions. All patients presented neutropenia of less than 300/mm3 and various kinds of infection resistant to antibiotic therapy. A favorable result was observed in 18 cases following these transfusions, which did not produce the secondary effects noted by others (chills, rash, fever, dyspnea). It was felt that this remarkable tolerance was a result of the collection procedure (elution at pH 7.4 ommission of centrifugation, thus securing the functional integrity of the cells). This impression was confirmed by the results of a battery of tests performed on the collected granulocytes, which included evaluation of their phagocytic and bacteriolytic functions and of their ability to break down a phagocytized antigen, together with measurements of lysosomial enzymes released in the supernatant.

Bacteriolysis↗

[Comprehensive evaluation and selection of urban eco-engineering virescent trees in Shenyang City].

Urban virescence eco-engineering is the core of urban eco-environmental construction, which can promote urban sustainable development. In urban virescence eco-engineering, the comprehensive evaluation of ecological adapt-ability and ecological effect of urban plants is the scientific basis of rational application and selection of urban garden plants. The ecological effect and integrative functions of urban virescence eco-engineering depend upon the selection and layout of garden plants. Using the methods of garden expert consultation and evaluation, this paper established systematically integrative evaluation and application indices of virescence plants in Shenyang City, from the aspects of ecological adaptability, ecological effect, beautification effect, resistance to plant diseases and insect pests, anti-pollution and economic results. According to garden experts evaluation and location of Shenyang, 200 sorts of virescence trees were evaluated and classified on the basis of the comprehensive evaluation system of virescence trees, and using cold resistance, drought resistance, barren resistance, plant diseases and insect pests resistance, anti-pollution, ornamental quality and ecological effects as the indexes. The results showed that the number of first rank trees was 58, the second was 93, methods of third was 38, and the fourth was 11, ranked by integrative performance.

China↗

[Blood cells at premature and physiological pregnancies].

Erythrocytes are integrated into the net of regulating mechanisms, having a significant importance in the course of pregnancy and together with nervous, endocrine and immune systems play an important task -- maintains functional integrity of the organism in changeable environment. Preparation for labor activities in women with physiological pregnancy begins with absolute normalization of rheological indices in order to maintain the homeostasis in stable state. As to premature pregnancy, here preparation of the organism for labor activities takes place without normalization of rheological indices, while stability of the homeostasis is supported by means of re-distribution of erythrocytes, increase of adhesion of erythrocytes with gigantic forms of thrombocytes, increase of amount of erythrocytes without central unstained areas, increase of HEB penetration, increase of adsorption, etc.

Adult↗

Electromechanical integration of cardiomyocytes derived from human embryonic stem cells.

Cell therapy is emerging as a promising strategy for myocardial repair. This approach is hampered, however, by the lack of sources for human cardiac tissue and by the absence of direct evidence for functional integration of donor cells into host tissues. Here we investigate whether cells derived from human embryonic stem (hES) cells can restore myocardial electromechanical properties. Cardiomyocyte cell grafts were generated from hES cells in vitro using the embryoid body differentiating system. This tissue formed structural and electromechanical connections with cultured rat cardiomyocytes. In vivo integration was shown in a large-animal model of slow heart rate. The transplanted hES cell-derived cardiomyocytes paced the hearts of swine with complete atrioventricular block, as assessed by detailed three-dimensional electrophysiological mapping and histopathological examination. These results demonstrate the potential of hES-cell cardiomyocytes to act as a rate-responsive biological pacemaker and for future myocardial regeneration strategies.

Animals↗

Interleukin-6 delays neutrophil apoptosis.

BACKGROUND: Neutrophil (PMN) apoptosis promotes the phagocytosis of PMNs without inciting an inflammatory response or local cytotoxic effect. This is important in the normal resolution of inflammatory processes and the control of tissue injury. Conversely, a delay in PMN apoptosis may facilitate PMN-mediated organ dysfunction by extending PMN functional integrity at an inflammatory site. Elevated circulating and tissue levels of interleukin-6 (IL-6) have been associated with postinjury organ dysfunction, and IL-6 appears to augment PMN cytotoxic functions. Therefore, we hypothesized that IL-6 delays PMN apoptosis, thereby enhancing PMN-mediated cytotoxicity. METHODS: Neutrophils isolated from healthy human donors were incubated for 24 hours in enriched RPMI 1640 cell culture medium at 37 degrees C in 5% carbon dioxide. Subgroups were incubated with IL-6, heat-denatured IL-6, or buffer alone. Apoptosis was assessed morphologically using acridine orange-ethidium bromide stain, and biochemically by DNA gel electrophoresis. Functional capacity of PMNs was assessed by superoxide generation after activation with phorbol myristate acetate or platelet-activating factor plus formyl-methionyl-leucyl-phenylalanine. RESULTS: Treatment with IL-6 resulted in a greater population of surviving (nonapopototic) PMNs after 24 hours. In addition, the IL-6-treated population produced more superoxide after 24 hours than did the untreated or heat-denature IL-6-treated groups, after either activating stimulus. CONCLUSIONS: Interleukin-6 delays PMN apoptosis, resulting in a larger population of surviving PMNs with a greater collective capacity for superoxide production. This could potentially facilitate PMN-mediated tissue injury and may be a mechanism whereby IL-6 contributes to organ dysfunction.

Apoptosis↗

Analysis of the Max-binding protein MNT in human medulloblastomas.

Medulloblastomas (MBs) are the most frequent malignant brain tumors in children. The molecular pathogenesis of these tumors is still poorly understood. Microsatellite and restriction-fragment-length polymorphism studies have revealed allelic loss of genetic material on the short arm of chromosome 17 in the region 17p13 in approximately 50% of MBs, suggesting the presence of a tumor-suppressor gene in this region. A candidate for this putative tumor-suppressor is the MNT gene, located at 17p13.3 and encoding a Max-interacting nuclear protein with transcriptional-repressor activity. In this study, we analyzed MNT mRNA and protein expression in 44 MB samples, including 32 primary tumors, 3 recurrent tumors and 9 MB cell lines. Allelic loss at 17p13.3 was found in 49% of informative cases. RT-PCR showed MNT mRNA expression in all cases analyzed. Endogenous Mnt protein with an apparent molecular weight of 72 to 74 kDa was detected in lysates from MB cell lines. The presence and functional integrity of Mnt in MBs were tested in electrophoretic mobility-shift assays. These experiments demonstrated that Mnt interacts with Max, and that this heterodimer binds DNA specifically, suggesting a functional bHLHZip domain of MB-derived Mnt. In support, single-strand conformation-polymorphism (SSCP) analyses revealed no mutation in the bHLHZip region. Deletion of the Mnt Sin3 interaction domain was shown to convert Mnt from an inhibitor of myc/ras-co-transformation into a molecule capable of cooperating with Ras in transformation. This region therefore was screened for mutation by SSCP: again, no alterations were found. These findings indicate that the MNT gene located at 17p13.3 is not likely to be involved in the molecular pathogenesis of MBs.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗

Transformation of Neurospora crassa with the trp-1 gene and the effect of host strain upon the fate of the transforming DNA.

Neurospora trp-1+ transformants, obtained by transforming a trp-1 inl strain with plasmid DNA containing the wild type trp1+ gene, were characterized by genetic and Southern blot analyses. The transforming trp-1 gene integrated at or near the resident site in all of the trp-1+ transformants obtained with circular DNA or DNA cut within the trp-1 coding region. The frequency of homologous integration decreased substantially when the donor DNA was cleaved outside the trp-1 coding region. The transformants were very stable mitotically and, in general, also showed meiotic stability. Analysis of trp-1+ transformants obtained with another recipient strain, trp-1+ ga-2 aro-9 inl, showed that homologous integration of donor DNA occurred in only 20% of the transformants, whether circular or linear DNA was used. Thus, the host strain employed for transformation appears to be a major factor in determining the fate of transforming DNA. Southern blot analysis of transformants showed that integration of the transforming DNA at the homologous site occurred by double crossover or gene conversion events rather than by insertion of the entire plasmid DNA. Multiple and apparently non functional integration events were observed in some transformants.

DNA Restriction Enzymes↗

[Principles of reorientation in triple arthrodesis].

Triple arthrodesis can be used for a three-dimensional correction of all types of hindfoot deformities. Prerequisites are a functional integrity of the ankle joint and an adequate bone stock. The procedure blocks the cardanic mechanism of the hindfoot and therefore reduces the shock-absorbing and mobile-adaptive functions of the foot. This results in increased stresses with the risk of long-term degenerative changes. In addition to triple arthrodesis, procedures to the forefoot are often necessary. Especially in neurogenic deformities, muscle lengthening and balancing procedures may be needed. In the evaluation of the results, different etiologies (e.g. posttraumatic, degenerative, neurogenic, congenital) and different deformities (varus, valgus, cavovarus, equinus) should not be mixed up. The results in congenital and neurogenic deformities in the literature are inferior to those of degenerative and posttraumatic origin. A standardization of indications, techniques, and evaluation criteria is still needed in order to exactly estimate the value of this procedure for different pathologies.

Arthrodesis↗

Modulations of input-output properties of corticospinal tract neurons by repetitive dynamic index finger abductions.

The goal of this study was to investigate how corticospinal tract neurons (CTNs) are modulated after repetitive dynamic muscle contractions. To address this question, changes of motor evoked potentials (MEPs) to transcranial magnetic stimulation and background EMG (B.EMG) activities were examined. Subjects were instructed to perform an isometric dynamic index finger abduction as accurately as possible under the target-force-matching tasks (10% or 30% MVC), while MEPs of a first dorsal interosseous (FDI) were elicited during performance of the task. After repetitive dynamic FDI contractions (100 trials), the following remarkable phenomena were observed: (1) both B.EMG activities and MEP amplitudes decreased in proportion to the number of trials, (2) these phenomena were most commonly observed in different conditions, i.e., different force levels and hands (preferred or non-preferred hands), and (3) after repetition of the tasks, the MEP amplitude/B.EMG (MEP/B.EMG) ratio became smaller. Decreases of B.EMG activities with reduction of MEP amplitudes and diminishing MEP/B.EMG ratio might suggest the occurrence of reorganization of input-output properties in CTNs for an efficient performance as a function of motor adaptation. Thus, we conclude that motor adaptation after repetitive dynamic muscle contractions probably occurs less specifically and due to susceptible modulations of spinal motoneurons reflected in the integrative functions of CTNs.

Adult↗

Effect of palmitate on hepatic biosynthetic functions at hyperthermic temperatures.

Livers of fasted rats were perfused for 80 min at 37 degrees-43 degrees C, supplemented with lactate, NH4Cl, and ornithine in the presence or absence of palmitate. Hepatic functional integrity was maintained from 37 degrees to 42 degrees C as assessed by gluconeogenesis, ureogenesis, and O2 consumption. Between 42 degrees and 43 degrees C a sharp decline in biosynthetic function occurred. The sharp decline in biosynthetic function occurred. The ratio of lactate disappearance to glucose formation increased progressively with increasing temperature when compared with the ratio obtained at 37 degrees C. Exogenous palmitate significantly decreased the ratio of lactate disappearance to glucose formation at 43 degrees C. Furthermore, palmitate attenuated the detrimental effects of hyperthermia on gluconeogenesis, ureogenesis, and O2 consumption found in the absence of palmitate. The 3-hydroxybutyrate/acetoacetate ratio progressively decreased as the liver temperature was increased in the presence or absence of palmitate, indicating a more oxidized mitochondrial redox state. Palmitate significantly increased the 3-hydroxybutyrate/acetoacetate ratio in the presence of gluconeogenic and ureogenic substrates at all temperatures examined. The data suggest that provision of fatty acid has a protective effect in thermally stressed liver. Moreover, palmitate may substitute for the increased energy requirements of the hyperthermic state.

Ammonium Chloride↗

Thymus-neuroendocrine-liver pathway.

In order to investigate the influence of the thymus on liver functions, we used adult thymectomized rats as a model and supplemented the animals with either thymic extracts or sex hormones. Male thymectomized rats exhibited a decrease in liver microsomal cytochrome P-450 and aminopyrine-N-demethylase activities. There was also a decrease in the levels of hypothalamic luteinizing hormone-releasing hormone (LHRH), plasma luteinizing hormone (LH) and testosterone. Supplementation of testosterone propionate to these animals restored their liver P-450 and demethylase activities to normal levels. Female thymectomized rats showed an increase of liver malondialdehyde (MDA), accompanied by a decrease of liver superoxide dismutase (SOD) and glutathione (GSH), and a decline of fluidity and calcium ion uptake in liver microsomal and mitochondrial membranes. There was also a decline in hypothalamic LHRH and plasma estradiol. Supplementation of thymic extract to female thymectomized rats decreased the liver MDA, increased the liver GSH, and restored the microsomal and mitochondrial membrane fluidity and calcium ion uptake. The decrease of liver MDA was also achieved by administration of estradiol benzoate. The data suggest that the thymus may influence liver functions through the hypothalamus-pituitary-gonad axis. Thus, a new 'thymus-neuroendocrine-liver pathway' is proposed that further affirms the significance of the thymus on maintaining homeostasis and integrative functions in the body.

Animals↗