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1. Repeated flashes of diffuse light were presented to the cat's eye over long periods of time (hours) while the mixed ganglion cell response was recorded from single axons in the optic tract. This was done for cats receiving gallamine triethiodide intravenously and for cats who did not receive the drug. 2. All responses were transformed into instantaneous pulse density tracings. Such tracings from control and gallamine cells were compared to observe possible effects of gallamine: (a) the shape (time course) did not change during gallamine administration; (b) maximum firing frequency, total number of spikes and latency was measured for both the on- and the off-component on the pulse density tracings and plotted versus time. Statistical methods failed to reveal any difference between the manner in which these response features of control cells and of gallamine cells varied with time.

Publisher Summary This chapter presents several examples of analog networks. The analog networks show how the retinal neurons could be wired so as to respond preferentially to some specific aspect of a stimulus. Similar considerations apply to other sensory modalities and to networks at higher centers in the nervous system. Within a retinal receptive field, one can expect to find a number of similar networks grouped together. For example, a contrast-detecting receptive field might consist of a number of units. All the units feed their signals into a ganglion cell through its dendritic field, and the ganglion cell response varies with stimulus position.

Human adenovirus types 6, 8, and 12 were immunosuppressive in chickens. A single intravenous injection of adenoviruses markedly depressed the 19 S hemolytic plaque-forming cell response in the spleen to the immunization with sheep red blood cells. Hemagglutinin production was also decreased in adenovirus type 6-infected chickens. Adenoviruses caused a transient immunosuppression in chickens which could be detected 2 to 3 days after the virus infection, and no depressive effect was found 16 to 20 days after virus injection. The possible mechanism of immunosuppression observed is discussed.

In nasal reconstruction applications, the response of cells to titanium (Ti) implants is largely determined by the surface characteristics of the implant. This study investigated an electrochemical anodization surface treatment intended to improve the response of primary human nasal epithelial cells (HNEpC) to Ti surfaces in nasal implant applications. We used a simple and fast electrochemical anodization treatment, i.e., applying anodic current, to produce a titanium dioxide (TiO2) nanonetwork layer on the Ti surface with average lateral pore size below 100 nm, depending on the current applied. The TiO2 nanonetwork layer exhibited enhanced hydrophilicity and protein adsorption ability compared with untreated Ti surfaces. In addition, the spreading morphology, cytoskeletal arrangement, and proliferation of HNEpC on the nanonetwork layer indicated excellent cell response characteristics. This research advances our understanding regarding the means by which a TiO2 nanonetwork layer can improve the response of HNEpC to Ti surfaces in nasal implant applications.

The analysis of live cells and tissue is gaining increasing importance in research and development. A number of demands are thus being made on the cultivation and analysis of cell response as well. For certain research approaches, in vitro three-dimensional (3D) cultivation best mimics natural conditions. Nevertheless, the imaging of such 3D environments is still a problem. To understand cell function in 3D, a number of in vivo imaging methods have been developed. This article introduces this field and proposes some interesting and promising imaging techniques for this approach.

It was found that interaction of a Nd:YAG laser beam with the Ti6Al4V alloy resulted in the wettability characteristics of the bio-metal improving. Such improvements in the wettability characteristics of the Ti6Al4V alloy were found to be due to: an increase in the surface roughness; and increase in the surface oxygen content and an increase in the polar component of the surface energy. From osteoblast cell response tests it was ascertained that cell adhesion and proliferation on the Nd:YAG laser treated Ti6Al4V alloy samples was considerably greater than on the untreated samples. By isolating the effects of surface roughness it was possible to confirm or refute the existence of a correlation between wettability characteristics and osteoblast cell bioactivity for the Nd:YAG laser treated Ti6Al4V alloy. The findings indicate that wettability characteristics (especially the surface oxygen content and the polar component of the surface energy) play an important role in promoting cell proliferation, particularly when surface roughness was simultaneously increased. Thus it was possible to conclude that the wettability characteristics of the Nd:YAG laser treated Ti6Al4V alloy were correlated to osteoblast cell bioactivity.It was found that interaction of a Nd:YAG laser beam with the Ti6Al4V alloy resulted in the wettability characteristics of the bio-metal improving. Such improvements in the wettability characteristics of the Ti6Al4V alloy were found to be due to: an increase in the surface roughness; and increase in the surface oxygen content and an increase in the polar component of the surface energy. From osteoblast cell response tests it was ascertained that cell adhesion and proliferation on the Nd:YAG laser treated Ti6Al4V alloy samples was considerably greater than on the untreated samples. By isolating the effects of surface roughness it was possible to confirm or refute the existence of a correlation between wettability characteristics and osteoblast cell bioactivity for the Nd:YAG laser treated Ti6Al4V alloy. The findings indicate that wettability characteristics (especially the surface oxygen content and the polar component of the surface energy) play an important role in promoting cell proliferation, particula...

Cytoskeletal filaments provide cells with mechanical stability and organization. The main key players are actin filaments and microtubules governing a cell’s response to mechanical stimuli. We investigated the specific influences of these crucial components by deforming MCF-7 epithelial cells at small (≤5% deformation) and large strains (>5% deformation). To understand specific contributions of actin filaments and microtubules, we systematically studied cellular responses after treatment with cytoskeleton influencing drugs. Quantification with the microfluidic optical stretcher allowed capturing the relative deformation and relaxation of cells under different conditions. We separated distinctive deformational and relaxational contributions to cell mechanics for actin and microtubule networks for two orders of magnitude of drug dosages. Disrupting actin filaments via latrunculin A, for instance, revealed a strain-independent softening. Stabilizing these filaments by treatment with jasplakinolide yielded cell softening for small strains but showed no significant change at large strains. In contrast, cells treated with nocodazole to disrupt microtubules displayed a softening at large strains but remained unchanged at small strains. Stabilizing microtubules within the cells via paclitaxel revealed no significant changes for deformations at small strains, but concentration-dependent impact at large strains. This suggests that for suspended cells, the actin cortex is probed at small strains, while at larger strains; the whole cell is probed with a significant contribution from the microtubules.

Background The purpose of this study was to address the affects of mood modifying drugs on the transcriptome, in a tissue culture model, using qPCR arrays as a cost effective approach to identifying regulatory networks and pathways that might coordinate the cell response to a specific drug.

Background To investigate glucose homeostasis in detail in Turner syndrome (TS), where impaired glucose tolerance (IGT) and type 2 diabetes are frequent. Methods Cross sectional study of women with Turner syndrome (TS)(n = 13) and age and body mass index matched controls (C) (n = 13), evaluated by glucose tolerance (oral and intravenous glucose tolerance test (OGTT and IVGTT)), insulin sensitivity (hyperinsulinemic, euglycemic clamp), beta-cell function (hyperglycaemic clamp, arginine and GLP-1 stimulation) and insulin pulsatility. Results Fasting glucose and insulin levels were similar. Higher glucose responses was seen in TS during OGTT and IVGTT, persisting after correction for body weight or muscle mass, while insulin responses were similar in TS and C, despite the higher glucose level in TS, leading to an insufficient increase in insulin response during dynamic testing. Insulin sensitivity was comparable in the two groups (TS vs. control: 8.6 ± 1.8 vs. 8.9 ± 1.8 mg/kg*30 min; p = 0.6), and the insulin responses to dynamic β-cell function tests were similar. Insulin secretion patterns examined by deconvolution analysis, approximate entropy, spectral analysis and autocorrelation analysis were similar. In addition we found low IGF-I, higher levels of cortisol and norepinephrine and an increased waist-hip ratio in TS. Conclusions Young normal weight TS women show significant glucose intolerance in spite of normal insulin secretion during hyperglycaemic clamping and normal insulin sensitivity. We recommend regularly testing for diabetes in TS. Trial Registration Registered with http://clinicaltrials.com, ID nr: NCT00419107

Induction of multispecific, functional CD4+ and CD8+ T cells is the immunological hallmark of acute self-limiting hepatitis C virus (HCV) infection in humans. In the present study, we showed that gene electrotransfer (GET) of a novel candidate DNA vaccine encoding an optimized version of the nonstructural region of HCV (from NS3 to NS5B) induced substantially more potent, broad, and long-lasting CD4+ and CD8+ cellular immunity than naked DNA injection in mice and in rhesus macaques as measured by a combination of assays, including IFN-γ ELISPOT, intracellular cytokine staining, and cytotoxic T cell assays. A protocol based on three injections of DNA with GET induced a substantially higher CD4+ T cell response than an adenovirus 6-based viral vector encoding the same Ag. To better evaluate the immunological potency and probability of success of this vaccine, we have immunized two chimpanzees and have compared vaccine-induced cell-mediated immunity to that measured in acute self-limiting infection in humans. GET of the candidate HCV vaccine led to vigorous, multispecific IFN-γ+CD8+ and CD4+ T lymphocyte responses in chimpanzees, which were comparable to those measured in five individuals that cleared spontaneously HCV infection. These data support the hypothesis that T cell responses elicited by the present strategy could be beneficial in prophylactic vaccine approaches against HCV.

The present investigation was carried out to study the cytological effects of the herbicide racer “flurochloridone” (3-chloro-4-(chloromethyl)-1-[3-(trifluoromethyl)= phenyl]-2-pyrrolidinone) on Allium cepa with respect to the cell response, mitotic index, mitotic abnormalities and chromosome aberrations. The roots of bulbs were treated with the following concentrations depending on the root growth inhibition test: 80 ppm (LD50), 40 ppm (LD50/2) and 20 ppm (LD50/4). The results indicated that flurochloridone herbicide reduced the mitotic division in A. cepa as compared to their control groups. The reduction in mitotic activity was more significant when the concentration of the herbicide increased and the exposure time was prolonged. The treatment conducted with flurochloridone induced a significant percentage of abnormal mitosis. Seven types of abnormalities were recorded: C-metaphase, laggards, stickiness, bridges, fragments, multipolarity and poliploidy. Micronucleated cells were also observed at interphase. In additon, in pretreated root tips, chromosome breaks, fragments and sister union were detected. © 2003 Taylor & Francis Group, LLC.

The environment around a cell during in vitro culture is unlikely to mimic those in vivo. Preliminary experiments with nanotopography have shown that nanoscale features can strongly influence cell morphology, adhesion, proliferation and gene regulation, but the mechanisms mediating this cell response remain unclear. In this perspective article, we attempt to illustrate that a possible mechanism is direct transmittal of forces encountered by cells during spreading to the nucleus via the cytoskeleton. We further try to illustrate that this 'self-induced' mechanotransduction may alter gene expression by changing interphase chromosome positioning. Whilst the observations described here to show how we think nanotopography can be developed as a tool to look at mechanotransduction are preliminary, we feel they indicate that topography may give cell biologists a non-invasive tool with which to investigate in vitro cellular mechanisms.

Atomic force microscopy has been introduced in the late 1980's in cellular biology to probe the mechanical response of living systems with a nanoscale resolution. However in traditional force-indentation curves obtained such a tool, the discrimination of elastic, viscous and dynamical aspects of a cell response under mechanical stress is very difficult, because it assumes that we have already designed a correct model to capture this response. Actually the response of a cell span different scales in space and in time. We propose here to revisit the interpretation of force-indentation curves without any a priori model to capture the temporal evolution of the shear modulus of living cells and compare this response to simple visco-elastic models. We show that using multi-scale analyzing tools such as wavelet transforms offers the possibility to survey in real time the different response modes of a cell during an indentation experiment.Because cells are also very different from one tissues to another one, we take cells with different adherence for this discussion; namely strongly adherent cells such a fibroblasts or myoblasts, circulating cells such as blood cells and intermediate cells that have also a very rich metabolic role such as hepatocytes.I acknowledge my collaborators in this work: namely Alain Arneodo, Benjamin Audit, Lotfi Berguiga, Elise Boyer-Provera, Simona Diguini, Guenola Drillon, Bastien Laperrousaz, Mael Le Berre, Veronique Maguer Satta, Cristina Martinez-Torres, Mathieu Piel, Laurent Schaeffer and Laura Streppa.

Skin fibroblasts were isolated from newborn spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) and cultured with 10% fetal calf serum. The growth rate, determined by the culture dish DNA content, was significantly higher in cells from SHR than from WKY in the presence of 10 and 15% serum. Re-initiation of DNA synthesis by serum and insulin was assessed by 24-h 3H-thymidine incorporation in quiescent cells. Serum (5, 10 and 15%) and insulin (1 microgram/ml) induced a marked stimulation of 3H-thymidine incorporation, and the cell response was significantly higher in SHR than in WKY for both agonists. These results indicate that the hyper-responsiveness to growth factors evident in newborn SHR skin fibroblasts is a genetic defect independent of haemodynamic changes.

Neutropenia is a well-known consequence of necrotizing enterocolitis in the newborn. Increased peripheral utilization or bone marrow suppression with systemic sepsis have been implicated as mechanisms for this neutropenia. However, many infants with NEC do not have positive blood cultures. We examined peritoneal as well as peripheral leukocyte counts at the time of surgery in 6 neonates with NEC.

An ROC analysis was performed on responses of single auditory‐nerve fibers (goldfish) and cochlear nucleus cells (gerbil) in order to predict intensity discrimination (in the goldfish and human) as a function of signal duration. To evaluate that the mean and variability of spike counts within single units account for psychophysical performance, spike number distributions were obtained (N = 100) for several durations (20 to 400 ms) and level differences (0.5–4 dB) at a unit's best frequency. The percent correct performance based on spike counts was found by generating ROC curves from empirical distributions and computing the area under the ROC [P(A)]. Theoretical psychometric functions were compared with psychometric functions from human and goldfish listeners obtained using a 21FC paradigm (human) and a rating method in classical respiratory conditioning (goldfish). The forms of the neural and psychophysical duration functions are similar in the mammal and the fish, but the fish shows higher thresholds compared with the human and with the neurophysiological predictions. In general, psychophysical performance is well modeled by the optimum processing of spike counts from individual cells. [Work supported by a Center Grant from NINCDS.]

The main purpose of this book is to depict the changes in fine structure found in disease. This difficult aim Dr. King has attempted within the remarkably short confines of 279 pages, including 97 plates. The 308 illustrations making up the plates comprise contributions from 173 investigators. In addition to an introduction relating some of the concepts of modern biology and pathology, there are 15 chapters. The first three considers cell structure, cell injury, and cell response; the remaining 12 cover a corresponding number of systems. Each chapter has an introductory series of statements about general pathologic processes or specific diseases, followed by several plates illustrating some of these changes. It is plainly impossible to cover comprehensively, in so little space, such a complex and heterogeneous mass of material. The result is a staccato presentation of some highlights and of some important concepts of disease. Of necessity, many of the

Of 171 patients having necrobiosis lipoidica diabeticorum (NLD), III had diabetes mellitus and 60 did not. Diabetic and nondiabetic patients had similar genetic backgrounds for diabetes mellitus, similar appearing lesions of NLD, and similar courses with respect to NLD. Of 19 initially nondiabetic patients, 42% had current or prospective diabetes mellitus on the basis of the results of standard and cortisone glucose tolerance tests. Many of those having normal responses to the tests gave family histories of diabetes mellitus. Patients having NLD usually develop diabetes mellitus at a younger age than usual. Both diseases may occur at any age however. NLD classically occurs as sclerodermiform plaques in the legs, but atypical lesions and locations occur. Palisading granuloma often characterized NLD lesions of diabetic patients and a histiocytic-epithelioid cell response, those of nondiabetic patients.

In: "Diseases of Poultry." (H. E. Biester and L. H. Schwarte, eds.) 4th ed. Iowa State University Press, Ames, Iowa, 1959. 4. Guillon, J. C., and I. Chouroulinkov. Les tumeurs renales chez le poulet. Economie et Medecine Animales 5: 238-247, 1964. 5. Ishiguro, H., D. Beard, J. R. Sommer, U. Heine, G. de The, and J. W. Beard. Multiplicity of cell response to the BAI strain A (myeloblastosis) avian tumor virus. I. Nephroblastoma (Wilms' tumor), gross and microscopic pathology. J. Natl. Cancer Inst. 29: 1-39, 1962. 6. Jackson, C. The incidence and pathology of tumours of domestic animals in South Africa. Onderstepoort J. Vet. Sci. 6: 349, 1936. 7. Jubb, K. V. F., and P. C. Kennedy. "Pathology of Domestic Animals." Volume 2. Academic Press, New York, 1963. 8. Mathews, F. P. Adenosarcomata of the kidneys of chickens. J. Am. Vet. Med. Assoc. 74: 238, 1929. 9. Mathews, F. P., and F. L. Walkey. Hypernephromas in the common fowl. J. Ann. Vet. Med. Assoc. 77: 218, 1930. 10. Smith, H. A., and T. C. Jones. "Veterinary Pathology." 2nd ed. Lea & Febiger, Philadelphia, 1961. 11. Willis, R. A. "The Borderland of Embryology and Pathology." Butterworths, Washington, D.C., pp. 432-435, 1962.

The ability to understand the mechanical properties of microalgae is extremely important in diverse applications. To obtain a better comprehension of algae cell response, we mechanically characterized single Scenedesmus dimorphus cells to understand their structural response. To accomplish this, we used atomic force microscopy to image dry S. dimorphus cells, which enabled us to map the AFM measurements to a location on the individual cells. We were then able to perform force measurements on the AFM to determine the Young's modulus of S. dimorphus. These findings are enabling us to understand mechanical properties of a single Scenedesmus dimorphus cell, which may be useful in areas such as energy.

This talk will provide an overview of new approaches to study and manipulate signaling in living cells and animals. Topics will include genetically encoded proteins that can be either activated or inactivated by light, multiplexing of biosensors using red shifted sensors combined with computational approaches, and novel methods to confer drug sensitivity on kinases. These tools are being used to understand how the dynamics of GTPase/adhesion signaling networks determine cell response to the extracellular matrix during trans-endothelial migration.