Radioimmunoassay and chromatographic similarity of circulating endogenous gonadotropin releasing hormone and hypothalamic extracts in man. [/sup 125/I tracer technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mortimer, C.H.; McNeilly, A.S.; Rees, L.H.

1976-10-01

A highly sensitive radioimmunoassay for the gonadotropin releasing hormone has been developed in order to study its physiological importance in man. In view of the expected low concentrations in peripheral blood, large volumes of human plasma were extracted by two different methods and the characteristics of the radioimmunoassayable material compared with those of synthetic decapeptide and extracts of human hypothalami. The results indicate that radioimmunoassayable gonadotropin releasing hormone is present in some human plasmas but the plasma concentrations are less than 2.5 pg/ml. Peripheral levels were more consistently measurable in women at midcycle and after the menopause. The hormone wasmore » undetectable in the plasma of normal men, human cerebrospinal fluid, and fetal cerebral tissue, but was present in fetal hypothalami.« less

Maternal T-Cell Engraftment Interferes With Human Leukocyte Antigen Typing in Severe Combined Immunodeficiency.

PubMed

Liu, Chang; Duffy, Brian; Bednarski, Jeffrey J; Calhoun, Cecelia; Lay, Lindsay; Rundblad, Barrett; Payton, Jacqueline E; Mohanakumar, Thalachallour

2016-02-01

To report the laboratory investigation of a case of severe combined immunodeficiency (SCID) with maternal T-cell engraftment, focusing on the interference of human leukocyte antigen (HLA) typing by blood chimerism. HLA typing was performed with three different methods, including sequence-specific primer (SSP), sequence-specific oligonucleotide, and Sanger sequencing on peripheral blood leukocytes and buccal cells, from a 3-month-old boy and peripheral blood leukocytes from his parents. Short tandem repeat (STR) testing was performed in parallel. HLA typing of the patient's peripheral blood leukocytes using the SSP method demonstrated three different alleles for each of the HLA-B and HLA-C loci, with both maternal alleles present at each locus. Typing results from the patient's buccal cells showed a normal pattern of inheritance for paternal and maternal haplotypes. STR enrichment testing of the patient's CD3+ T lymphocytes and CD15+ myeloid cells confirmed maternal T-cell engraftment, while the myeloid cell profile matched the patient's buccal cells. Maternal T-cell engraftment may interfere with HLA typing in patients with SCID. Selection of the appropriate typing methods and specimens is critical for accurate HLA typing and immunologic assessment before allogeneic hematopoietic stem cell transplantation. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Distribution of subpopulations of dendritic cells in peripheral blood of patients treated with exogenous thyrotropin

PubMed Central

2012-01-01

Background Dendritic cells (DCs) play a major role as regulators of inflammatory events associated with thyroid pathology. The immunoregulatory function of DCs depends strongly on their subtype, as well as maturation and activation status. Numerous hormonal factors modulate the immune properties of DCs, however, little is known about effects exerted by the hypothalamus-pituitary-thyroid-axis. Recently, we have shown a direct regulatory influence of thyroid hormones (TH) on human DCs function. The aim of the present study was to analyze the effect of systemically administered thyrotropin (TSH) on human blood DCs ex vivo. Methods Blood samples for the cytometric analysis of peripheral blood plasmacytoid and myeloid DCs subtypes were collected from patients subjected to total thyroidectomy because of differentiated thyroid carcinoma at 2 time points: (i) directly before the commencement of TSH administration and (ii) 5 days after first TSH injection. The whole blood quantitative and phenotypic analysis of plasmacytoid and myeloid DCs subtypes was performed by flow cytometry. Results Administration of TSH did not influence the percentage of plasmacytoid DCs in peripheral blood of study participants. Also the percentage of the two main myeloid DCs subpopulations – CD1c/BDCA1+ DCs and CD141/BDCA3+ DCs did not change significantly. TSH administration had no effect on the surface expression of CD86 – one of the major costimulatory molecules – neither in the whole peripheral blood mononuclear cell (PBMC) fraction nor in particular DCs subtypes. Conclusions In the present study, we demonstrated no influence of systemic TSH administration on human peripheral blood DCs subtypes. These results are in accordance with our previous work suggesting the direct effect of TH on human DCs ex vivo. PMID:23199104

A novel method to generate and culture human mast cells: Peripheral CD34+ stem cell-derived mast cells (PSCMCs).

PubMed

Schmetzer, Oliver; Valentin, Patricia; Smorodchenko, Anna; Domenis, Rossana; Gri, Giorgia; Siebenhaar, Frank; Metz, Martin; Maurer, Marcus

2014-11-01

The identification and characterization of human mast cell (MC) functions are hindered by the shortage of MC populations suitable for investigation. Here, we present a novel technique for generating large numbers of well differentiated and functional human MCs from peripheral stem cells (=peripheral stem cell-derived MCs, PSCMCs). Innovative and key features of this technique include 1) the use of stem cell concentrates, which are routinely discarded by blood banks, as the source of CD34+ stem cells, 2) cell culture in serum-free medium and 3) the addition of LDL as well as selected cytokines. In contrast to established and published protocols that use CD34+ or CD133+ progenitor cells from full blood, we used a pre-enriched cell population obtained from stem cell concentrates, which yielded up to 10(8) differentiated human MCs per batch after only three weeks of culture starting with 10(6) total CD34+ cells. The total purity on MCs (CD117+, FcεR1+) generated by this method varied between 55 and 90%, of which 4-20% were mature MCs that contain tryptase and chymase and show expression of FcεRI and CD117 in immunohistochemistry. PSCMCs showed robust histamine release in response to stimulation with anti-FcεR1 or IgE/anti-IgE, and increased proliferation and differentiation in response to IL-1β or IFN-γ. Taken together, this new protocol of the generation of large numbers of human MCs provides for an innovative and suitable option to investigate the biology of human MCs. Copyright © 2014 Elsevier B.V. All rights reserved.

A novel method for measuring hydraulic conductivity at the human blood-nerve barrier in vitro.

PubMed

Helton, E Scott; Palladino, Steven; Ubogu, Eroboghene E

2017-01-01

Microvascular barrier permeability to water is an essential biophysical property required for the homeostatic maintenance of unique tissue microenvironments. This is of particular importance in peripheral nerves where strict control of ionic concentrations is needed for axonal signal transduction. Previous studies have associated inflammation, trauma, toxin exposure and metabolic disease with increases in water influx and hydrostatic pressure in peripheral nerves with resultant endoneurial edema that may impair axonal function. The regulation of water permeability across endoneurial microvessels that form the blood-nerve barrier (BNB) is poorly understood. Variations exist in apparatus and methods used to measure hydraulic conductivity. The objective of the study was to develop a simplified hydraulic conductivity system using commercially available components to evaluate the BNB. We determined the mean hydraulic conductivity of cultured confluent primary and immortalized human endoneurial endothelial cell layers as 2.00×10 -7 and 2.17×10 -7 cm/s/cm H₂O respectively, consistent with restrictive microvascular endothelial cells in vitro. We also determined the mean hydraulic conductivity of immortalized human brain microvascular endothelial cell layers, a commonly used blood-brain barrier (BBB) cell line, as 0.20×10 -7 cm/s/cm H₂O, implying a mean 10-fold higher resistance to transendothelial water flux in the brain compared to peripheral nerves. To our knowledge, this is the first reported measurement of human BNB and BBB hydraulic conductivities. This model represents an important tool to further characterize the human BNB and deduce the molecular determinants and signaling mechanisms responsible for BNB hydraulic conductivity in normal and disease states in vitro. Copyright © 2016 Elsevier Inc. All rights reserved.

Ocular surface epithelium induces expression of human mucosal lymphocyte antigen (HML-1) on peripheral blood lymphocytes

PubMed Central

Gomes, J A P; Dua, H S; Rizzo, L V; Nishi, M; Joseph, A; Donoso, L A

2004-01-01

Background/aims: Peripheral blood CD8+ lymphocytes that home to mucosal surfaces express the human mucosal lymphocyte antigen (HML-1). At mucosal surfaces, including the ocular surface, only intraepithelial CD8+ lymphocytes express HML-1. These lymphocytes are retained in the intraepithelial compartment by virtue of the interaction between HML-1 and its natural ligand, E-cadherin, which is expressed on epithelial cells. The purpose of this study was to determine whether ocular surface epithelial cells (ocular mucosa) could induce the expression of human mucosal lymphocyte antigen on peripheral blood lymphocytes. Methods: Human corneal and conjunctival epithelial cells were co-cultured with peripheral blood lymphocytes. Both non-activated and activated lymphocytes were used in the experiments. After 7 days of incubation, lymphocytes were recovered and analysed for the antigens CD8/HML-1, CD4/HML-1, CD3/CD8, CD3/CD4, CD3/CD25, CD8/CD25, and CD4/CD25 by flowcytometry. Results: Significant statistical differences were observed in the CD8/HML-1 expression when conjunctival epithelial cells were co-cultured with non-activated and activated lymphocytes (p = 0.04 for each) and when corneal epithelial cells were co-cultured with non-activated lymphocytes (p = 0.03). Significant statistical difference in CD4/HML-1 expression was observed only when conjunctival epithelial cells were co-cultured with activated lymphocytes (p = 0.02). Conclusion: Ocular surface epithelial cells can induce the expression of human mucosal lymphocyte antigen on CD8+ (and to some extent on CD4+) lymphocytes. This may allow the retention of CD8+ and CD4+ lymphocytes within the epithelial compartment of the conjunctiva and play a part in mucosal homing of lymphocytes. PMID:14736792

Noninvasive method for assessing the human circadian clock using hair follicle cells

PubMed Central

Akashi, Makoto; Soma, Haruhiko; Yamamoto, Takuro; Tsugitomi, Asuka; Yamashita, Shiko; Yamamoto, Takuya; Nishida, Eisuke; Yasuda, Akio; Liao, James K.; Node, Koichi

2010-01-01

A thorough understanding of the circadian clock requires qualitative evaluation of circadian clock gene expression. Thus far, no simple and effective method for detecting human clock gene expression has become available. This limitation has greatly hampered our understanding of human circadian rhythm. Here we report a convenient, reliable, and less invasive method for detecting human clock gene expression using biopsy samples of hair follicle cells from the head or chin. We show that the circadian phase of clock gene expression in hair follicle cells accurately reflects that of individual behavioral rhythms, demonstrating that this strategy is appropriate for evaluating the human peripheral circadian clock. Furthermore, using this method, we indicate that rotating shift workers suffer from a serious time lag between circadian gene expression rhythms and lifestyle. Qualitative evaluation of clock gene expression in hair follicle cells, therefore, may be an effective approach for studying the human circadian clock in the clinical setting. PMID:20798039

A Simple Mouse Model for the Study of Human Immunodeficiency Virus.

PubMed

Kim, Kang Chang; Choi, Byeong-Sun; Kim, Kyung-Chang; Park, Ki Hoon; Lee, Hee Jung; Cho, Young Keol; Kim, Sang Il; Kim, Sung Soon; Oh, Yu-Kyoung; Kim, Young Bong

2016-02-01

Humanized mouse models derived from immune-deficient mice have been the primary tool for studies of human infectious viruses, such as human immunodeficiency virus (HIV). However, the current protocol for constructing humanized mice requires elaborate procedures and complicated techniques, limiting the supply of such mice for viral studies. Here, we report a convenient method for constructing a simple HIV-1 mouse model. Without prior irradiation, NOD/SCID/IL2Rγ-null (NSG) mice were intraperitoneally injected with 1 × 10(7) adult human peripheral blood mononuclear cells (hu-PBMCs). Four weeks after PBMC inoculation, human CD45(+) cells, and CD3(+)CD4(+) and CD3(+)CD8(+) T cells were detected in peripheral blood, lymph nodes, spleen, and liver, whereas human CD19(+) cells were observed in lymph nodes and spleen. To examine the usefulness of hu-PBMC-inoculated NSG (hu-PBMC-NSG) mice as an HIV-1 infection model, we intravenously injected these mice with dual-tropic HIV-1DH12 and X4-tropic HIV-1NL4-3 strains. HIV-1-infected hu-PBMC-NSG mice showed significantly lower human CD4(+) T cell counts and high HIV viral loads in the peripheral blood compared with noninfected hu-PBMC-NSG mice. Following highly active antiretroviral therapy (HAART) and neutralizing antibody treatment, HIV-1 replication was significantly suppressed in HIV-1-infected hu-PBMC-NSG mice without detectable viremia or CD4(+) T cell depletion. Moreover, the numbers of human T cells were maintained in hu-PBMC-NSG mice for at least 10 weeks. Taken together, our results suggest that hu-PBMC-NSG mice may serve as a relevant HIV-1 infection and pathogenesis model that could facilitate in vivo studies of HIV-1 infection and candidate HIV-1 protective drugs.

A Protein Structure Initiative Approach to Expression, Purification, and In Situ Delivery of Human Cytochrome b5 to Membrane Vesicles†

PubMed Central

Sobrado, Pablo; Goren, Michael A.; James, Declan; Amundson, Carissa K.; Fox, Brian G.

2008-01-01

A specialized vector backbone from the Protein Structure Initiative was used to express full-length human cytochrome b5 as a C-terminal fusion to His8-maltose binding protein in Escherichia coli. The fusion protein could be completely cleaved by tobacco etch virus protease, and a yield of ~18 mg of purified full-length human cytochrome b5 per liter of culture medium was obtained (2.3 mg per]of wet weight bacterial cells). In situ proteolysis of the fusion protein in the presence of chemically defined synthetic liposomes allowed facile spontaneous delivery of the functional peripheral membrane protein into a defined membrane environment without prior exposure to detergents or other lipids. The utility of this approach as a delivery method for production and incorporation of monotopic (peripheral) membrane proteins is discussed. PMID:18226920

A Protein Structure Initiative approach to expression, purification, and in situ delivery of human cytochrome b5 to membrane vesicles.

PubMed

Sobrado, Pablo; Goren, Michael A; James, Declan; Amundson, Carissa K; Fox, Brian G

2008-04-01

A specialized vector backbone from the Protein Structure Initiative was used to express full-length human cytochrome b5 as a C-terminal fusion to His8-maltose binding protein in Escherichia coli. The fusion protein could be completely cleaved by tobacco etch virus protease, and a yield of approximately 18 mg of purified full-length human cytochrome b5 per liter of culture medium was obtained (2.3mg per g of wet weight bacterial cells). In situ proteolysis of the fusion protein in the presence of chemically defined synthetic liposomes allowed facile spontaneous delivery of the functional peripheral membrane protein into a defined membrane environment without prior exposure to detergents or other lipids. The utility of this approach as a delivery method for production and incorporation of monotopic (peripheral) membrane proteins is discussed.

Micro-buffy coats of whole blood: a method for the electron microscopic study of mononuclear cells.

PubMed

Nunes, J F; Soares, J O; Alves de Matos, A P

1979-09-01

A method for the electron microscopic study of human peripheral lymphocytes by which very small buffy coats are obtained through centrifugation of heparinized whole blood in glass or plastic microhematocrit tubes is presented. This method is time saving and efficient, yielding well preserved material and a comparatively large number of mononuclear cells (mainly lymphocytes) in each thin section.

Stimulating effect of thyroid hormones in peripheral nerve regeneration: research history and future direction toward clinical therapy

PubMed Central

Barakat-Walter, I.; Kraftsik, R.

2018-01-01

Injury to peripheral nerves is often observed in the clinic and severe injuries may cause loss of motor and sensory functions. Despite extensive investigation, testing various surgical repair techniques and neurotrophic molecules, at present, a satisfactory method to ensuring successful recovery does not exist. For successful molecular therapy in nerve regeneration, it is essential to improve the intrinsic ability of neurons to survive and to increase the speed of axonal outgrowth. Also to induce Schwann cell phenotypical changes to prepare the local environment favorable for axonal regeneration and myelination. Therefore, any molecule that regulates gene expression of both neurons and Schwann cells could play a crucial role in peripheral nerve regeneration. Clinical and experimental studies have reported that thyroid hormones are essential for the normal development and function of the nervous system, so they could be candidates for nervous system regeneration. This review provides an overview of studies devoted to testing the effect of thyroid hormones on peripheral nerve regeneration. Also it emphasizes the importance of combining biodegradable tubes with local administration of triiodothyronine for future clinical therapy of human severe injured nerves. We highlight that the local and single administration of triiodothyronine within biodegradable nerve guide improves significantly the regeneration of severed peripheral nerves, and accelerates functional recovering. This technique provides a serious step towards future clinical application of triiodothyronine in human severe injured nerves. The possible regulatory mechanism by which triiodothyronine stimulates peripheral nerve regeneration is a rapid action on both axotomized neurons and Schwann cells. PMID:29722302

Genotoxicity in primary human peripheral lymphocytes after exposure to lithium titanate nanoparticles in vitro.

PubMed

Akbaba, Giray B; Turkez, Hasan; Sönmez, Erdal; Tatar, Abdulgani; Yilmaz, Mehmet

2016-08-01

Lithium titanate (Li 2 TiO 3 ) nanoparticles (LTT NPs; <100 nm) are widely used in battery technology, porcelain enamels, and ceramic insulating bodies. With the increased applications of LTT NPs, the concerns about their potential human toxicity effects and their environmental impact were also increased. However, toxicity data for LTT NPs relating to human health are very limited. Therefore, the purpose of this study was to evaluate whether LTT NPs are able to induce genetic damage in human peripheral lymphocytes in vitro when taking into consideration that DNA damage plays an important role in carcinogenesis. With this aim, the chromosome aberrations (CA), sister chromatid exchanges (SCE), and micronucleus (MN) assays were used as genotoxicity end points. Human peripheral lymphocytes obtained from five healthy male volunteers were exposed to LTT NPs at final dispersed concentrations ranging from 0 to 1000 μg/mL for 72 h at 37°C. The obtained results indicated that LTT NPs compound did not induce DNA damage in human peripheral lymphocytes as depicted by CA/cell, SCE/cell, and MN/1000 cell values in all concentrations tested. In summary, our results revealed that exposure to LTT NPs is not capable of inducing DNA lesions in human peripheral lymphocytes for the first time. © The Author(s) 2014.

Novel wave intensity analysis of arterial pulse wave propagation accounting for peripheral reflections

PubMed Central

Alastruey, Jordi; Hunt, Anthony A E; Weinberg, Peter D

2014-01-01

We present a novel analysis of arterial pulse wave propagation that combines traditional wave intensity analysis with identification of Windkessel pressures to account for the effect on the pressure waveform of peripheral wave reflections. Using haemodynamic data measured in vivo in the rabbit or generated numerically in models of human compliant vessels, we show that traditional wave intensity analysis identifies the timing, direction and magnitude of the predominant waves that shape aortic pressure and flow waveforms in systole, but fails to identify the effect of peripheral reflections. These reflections persist for several cardiac cycles and make up most of the pressure waveform, especially in diastole and early systole. Ignoring peripheral reflections leads to an erroneous indication of a reflection-free period in early systole and additional error in the estimates of (i) pulse wave velocity at the ascending aorta given by the PU–loop method (9.5% error) and (ii) transit time to a dominant reflection site calculated from the wave intensity profile (27% error). These errors decreased to 1.3% and 10%, respectively, when accounting for peripheral reflections. Using our new analysis, we investigate the effect of vessel compliance and peripheral resistance on wave intensity, peripheral reflections and reflections originating in previous cardiac cycles. PMID:24132888

Generation of Human Induced Pluripotent Stem Cells from Peripheral Blood Mononuclear Cells Using Sendai Virus.

PubMed

Soares, Filipa A C; Pedersen, Roger A; Vallier, Ludovic

2016-01-01

This protocol describes the efficient isolation of peripheral blood mononuclear cells from circulating blood via density gradient centrifugation and subsequent generation of integration-free human induced pluripotent stem cells. Peripheral blood mononuclear cells are cultured for 9 days to allow expansion of the erythroblast population. The erythroblasts are then used to derive human induced pluripotent stem cells using Sendai viral vectors, each expressing one of the four reprogramming factors Oct4, Sox2, Klf4, and c-Myc.

Development of ultrasonic methods for hemodynamic measurements

NASA Technical Reports Server (NTRS)

Histand, M. B.; Miller, C. W.; Wells, M. K.; Mcleod, F. D.; Greene, E. R.; Winter, D.

1975-01-01

A transcutanous method to measure instantaneous mean blood flow in peripheral arteries of the human body was defined. Transcutanous and implanted cuff ultrasound velocity measurements were evaluated, and the accuracies of velocity, flow, and diameter measurements were assessed for steady flow. Performance criteria were established for the pulsed Doppler velocity meter (PUDVM), and performance tests were conducted. Several improvements are suggested.

Visualization of peripheral vasodilative indices in human skin by use of red, green, blue images

NASA Astrophysics Data System (ADS)

Nishidate, Izumi; Tanaka, Noriyuki; Kawase, Tatsuya; Maeda, Takaaki; Yuasa, Tomonori; Aizu, Yoshihisa; Yuasa, Tetsuya; Niizeki, Kyuichi

2013-06-01

We propose a method to visualize the arterial inflow, the vascular resistance, and the venous capacitance in the skin tissue from red, green, blue (RGB) digital color images. The arterial inflow and the venous capacitance in the skin tissue are visualized based on an increase in the rate of change in the total blood concentration and the change of the total blood concentration during upper limb occlusion at a pressure of 50 mmHg. The resultant arterial inflow with the measured mean arterial pressure also provides an image of the vascular resistance in human skin. The arterial inflow, the vascular resistance, and the venous capacitance acquired by the method are well correlated with those obtained from the conventional strain-gauge plethysmograph. The correlation coefficients R between the estimated values by the method and the measurements by the SPG are calculated to be 0.83 (P<0.001) for the arterial inflow, 0.77 (P<0.01) for the vascular resistance, and 0.77 (P<0.01) for the venous capacitance. The arterial inflow and the venous capacitance in the skin tissue are significantly higher in active subjects compared with the sedentary subjects, whereas the vascular resistance was significantly lower in the active subjects compared with the sedentary subjects. The results of the present study indicate the possibility of using the proposed method for evaluating the peripheral vascular functions in human skin.

The Effect of Spectacle Lenses Containing Peripheral Defocus on Refractive Error and Horizontal Eye Shape in the Guinea Pig

PubMed Central

E. Bowrey, Hannah; Zeng, Guang; Y. Tse, Dennis; J. Leotta, Amelia; Wu, Yi; To, Chi-Ho; F. Wildsoet, Christine; McFadden, Sally A.

2017-01-01

Purpose It has been proposed that the peripheral retina, responding to local optical defocus, contributes to myopia and associated altered eye growth in humans. To test this hypothesis, we measured the changes in central (on-axis) and peripheral ocular dimensions in guinea pigs wearing a concentric bifocal spectacle lens design with power restricted to the periphery. Methods Five groups of guinea pigs (n = 83) wore either a unifocal (UF) spectacle lens (−4, 0, or +4 Diopters [D]), or a peripheral defocus (PF) spectacle lens that had a plano center (diameter of 5 mm) with either −4 or +4 D in the surround (−4/0 or +4/0 D). The overall optical diameter of all lenses was 12 mm. Lenses were worn over one eye from 8 to 18 days of age for negative and plano lenses, or from 8 to 22 days of age for positive lenses. Refractive error was measured centrally and 30° off-axis in the temporal and nasal retina. The shape of the eye was analyzed from images of sectioned eyes. Results Lenses of −4 D UF induced myopia, reflecting enhanced ocular elongation, which was centered on the optic nerve head and included the surrounding peripapillary zone (PPZ, 18° in diameter). Some ocular expansion, including within the PPZ, also was recorded with −4/0 and +4/0 D PF lenses while the +4 D UF lens inhibited rather than enhanced elongation, centrally and peripherally. Conclusions Peripheral defocus-induced ocular expansion encompasses the PPZ, irrespective of the sign of the inducing defocus. Understanding the underlying mechanism potentially has important implications for designing multifocal lenses for controlling myopia in humans and also potentially for understanding the link between myopia and glaucoma. PMID:28549092

Human psychophysics and rodent spinal neurones exhibit peripheral and central mechanisms of inflammatory pain in the UVB and UVB heat rekindling models.

PubMed

O'Neill, Jessica; Sikandar, Shafaq; McMahon, Stephen B; Dickenson, Anthony H

2015-09-01

Translational research is key to bridging the gaps between preclinical findings and the patients, and a translational model of inflammatory pain will ideally induce both peripheral and central sensitisation, more effectively mimicking clinical pathophysiology in some chronic inflammatory conditions. We conducted a parallel investigation of two models of inflammatory pain, using ultraviolet B (UVB) irradiation alone and UVB irradiation with heat rekindling. We used rodent electrophysiology and human quantitative sensory testing to characterise nociceptive processing in the peripheral and central nervous systems in both models. In both species, UVB irradiation produces peripheral sensitisation measured as augmented evoked activity of rat dorsal horn neurones and increased perceptual responses of human subjects to mechanical and thermal stimuli. In both species, UVB with heat rekindling produces central sensitisation. UVB irradiation alone and UVB with heat rekindling are translational models of inflammation that produce peripheral and central sensitisation, respectively. The predictive value of laboratory models for human pain processing is crucial for improving translational research. The discrepancy between peripheral and central mechanisms of pain is an important consideration for drug targets, and here we describe two models of inflammatory pain that involve ultraviolet B (UVB) irradiation, which can employ peripheral and central sensitisation to produce mechanical and thermal hyperalgesia in rats and humans. We use electrophysiology in rats to measure the mechanically- and thermally-evoked activity of rat spinal neurones and quantitative sensory testing to assess human psychophysical responses to mechanical and thermal stimulation in a model of UVB irradiation and in a model of UVB irradiation with heat rekindling. Our results demonstrate peripheral sensitisation in both species driven by UVB irradiation, with a clear mechanical and thermal hypersensitivity of rat dorsal horn neurones and enhanced perceptual responses of human subjects to both mechanical and thermal stimulation. Additional heat rekindling produces markers of central sensitisation in both species, including enhanced receptive field sizes. Importantly, we also showed a correlation in the evoked activity of rat spinal neurones to human thermal pain thresholds. The parallel results in rats and humans validate the translational use of both models and the potential for such models for preclinical assessment of prospective analgesics in inflammatory pain states. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Initial analysis of peripheral lymphocytic extracellular signal related kinase activation in autism

PubMed Central

Erickson, Craig A.; Ray, Balmiki; Wink, Logan K.; Bayon, Baindu L.; Pedapati, Ernest V.; Shaffer, Rebecca; Schaefer, Tori L.; Lahiri, Debomoy K.

2018-01-01

Background Dysregulation of extracellular signal-related kinase (ERK) activity has been potentially implicated in the pathophysiology of autistic disorder (autism). ERK is part of a central intracellular signaling cascade responsible for a myriad of cellular functions. ERK is expressed in peripheral blood lymphocytes, and measurement of activated (phosphorylated) lymphocytic ERK is commonly executed in many areas of medicine. We sought to conduct the first study of ERK activation in humans with autism by utilizing a lymphocytic ERK activation assay. We hypothesized that ERK activation would be enhanced in peripheral blood lymphocytes from persons with autism compared to those of neurotypical control subjects. Method We conducted an initial study of peripheral lymphocyte ERK activation in 45 subjects with autism and 26 age- and gender-matched control subjects (total n = 71). ERK activation was measured using a lymphocyte counting method (primary outcome expressed as lymphocytes staining positive for cytosolic phosphorylated ERK divided by total cells counted) and additional Western blot analysis of whole cell phosphorylated ERK adjusted for total ERK present in the lymphocyte lysate sample. Results Cytosolic/nuclear localization of pERK activated cells were increased by almost two-fold in the autism subject group compared to matched neurotypical control subjects (cell count ratio of 0.064 ± 0.044 versus 0.034 ± 0.031; p = 0.002). Elevated phosphorylated ERK levels in whole cell lysates also showed increased activated ERK in the autism group compared to controls (n = 54 total) in Western blot analysis. Conclusions The results of this first in human ERK activation study are consistent with enhanced peripheral lymphocytic ERK activation in autism, as well as suggesting that cellular compartmentalization of activated ERK may be altered in this disorder. Future work will be required to explore the impact of concomitant medication use and other subject characteristics such as level of cognitive functioning on ERK activation. Trial Registration Not applicable. PMID:27743527

Separation of lymphocytes by electrophoresis under terrestrial conditions and at zero gravity

NASA Technical Reports Server (NTRS)

Rubin, A. L.

1977-01-01

Electrophoretic mobility (EPM) of human peripheral lymphocytes were examined with the following objectives: To determine differences in EPM of lymphocytes under immuno-stimulated and immuno-suppressed states. To define the conditions necessary for the separation of lymphocyte sub-populations in normal and pathological conditions; To investigate immunological active, charged chemical groups on lymphocyte surfaces; and to investigate pathophysiological mechanisms of immune responsiveness, as reflected by alterations in EPM. To evaluate the potential of lymphocyte electrophoresis as: (1) a means of monitoring the immune status of kidney transplant recipients, (2) in predicting the outcome of kidney transplants, and (3) as a method for separation of lymphocyte sub-populations, the EPM was studied for unfractionated human peripheral lymphocytes and of populations enriched with T and "B" cells from normal adults, hemodialysis patients and kidney transplant recipients.

Visual information without thermal energy may induce thermoregulatory-like cardiovascular responses

PubMed Central

2013-01-01

Background Human core body temperature is kept quasi-constant regardless of varying thermal environments. It is well known that physiological thermoregulatory systems are under the control of central and peripheral sensory organs that are sensitive to thermal energy. If these systems wrongly respond to non-thermal stimuli, it may disturb human homeostasis. Methods Fifteen participants viewed video images evoking hot or cold impressions in a thermally constant environment. Cardiovascular indices were recorded during the experiments. Correlations between the ‘hot-cold’ impression scores and cardiovascular indices were calculated. Results The changes of heart rate, cardiac output, and total peripheral resistance were significantly correlated with the ‘hot-cold’ impression scores, and the tendencies were similar to those in actual thermal environments corresponding to the impressions. Conclusions The present results suggest that visual information without any thermal energy can affect physiological thermoregulatory systems at least superficially. To avoid such ‘virtual’ environments disturbing human homeostasis, further study and more attention are needed. PMID:24373765

The miRNA and mRNA Signatures of Peripheral Blood Cells in Humans Infected with Trypanosoma brucei gambiense.

PubMed

Lueong, Smiths; Leong, Smiths; Simo, Gustave; Camara, Mamadou; Jamonneau, Vincent; Kabore, Jacques; Ilboudo, Hamidou; Bucheton, Bruno; Hoheisel, Jörg D; Clayton, Christine

2013-01-01

Simple, reliable tools for diagnosis of human African Trypanosomiases could ease field surveillance and enhance patient care. In particular, current methods to distinguish patients with (stage II) and without (stage I) brain involvement require samples of cerebrospinal fluid. We describe here an exploratory study to find out whether miRNAs from peripheral blood leukocytes might be useful in diagnosis of human trypanosomiasis, or for determining the stage of the disease. Using microarrays, we measured miRNAs in samples from Trypanosoma brucei gambiense-infected patients (9 stage I, 10 stage II), 8 seronegative parasite-negative controls and 12 seropositive, but parasite-negative subjects. 8 miRNAs (out of 1205 tested) showed significantly lower expression in patients than in seronegative, parasite-negative controls, and 1 showed increased expression. There were no clear differences in miRNAs between patients in different disease stages. The miRNA profiles could not distinguish seropositive, but parasitologically negative samples from controls and results within this group did not correlate with those from the trypanolysis test. Some of the regulated miRNAs, or their predicted mRNA targets, were previously reported changed during other infectious diseases or cancer. We conclude that the changes in miRNA profiles of peripheral blood lymphocytes in human African trypanosomiasis are related to immune activation or inflammation, are probably disease-non-specific, and cannot be used to determine the disease stage. The approach has little promise for diagnostics but might yield information about disease pathology.

Large-Scale Culture and Genetic Modification of Human Natural Killer Cells for Cellular Therapy.

PubMed

Lapteva, Natalia; Parihar, Robin; Rollins, Lisa A; Gee, Adrian P; Rooney, Cliona M

2016-01-01

Recent advances in methods for the ex vivo expansion of human natural killer (NK) cells have facilitated the use of these powerful immune cells in clinical protocols. Further, the ability to genetically modify primary human NK cells following rapid expansion allows targeting and enhancement of their immune function. We have successfully adapted an expansion method for primary NK cells from peripheral blood mononuclear cells or from apheresis products in gas permeable rapid expansion devices (G-Rexes). Here, we describe an optimized protocol for rapid and robust NK cell expansion as well as a method for highly efficient retroviral transduction of these ex vivo expanded cells. These methodologies are good manufacturing practice (GMP) compliant and could be used for clinical-grade product manufacturing.

Susceptibility Testing by Polymerase Chain Reaction DNA Quantitation: A Method to Measure Drug Resistance of Human Immunodeficiency Virus Type 1 Isolates

NASA Astrophysics Data System (ADS)

Eron, Joseph J.; Gorczyca, Paul; Kaplan, Joan C.; D'Aquila, Richard T.

1992-04-01

Polymerase chain reaction (PCR) DNA quantitation (PDQ) susceptibility testing rapidly and directly measures nucleoside sensitivity of human immunodeficiency virus type 1 (HIV-1) isolates. PCR is used to quantitate the amount of HIV-1 DNA synthesized after in vitro infection of peripheral blood mononuclear cells. The relative amounts of HIV-1 DNA in cell lysates from cultures maintained at different drug concentrations reflect drug inhibition of virus replication. The results of PDQ susceptibility testing of 2- or 3-day cultures are supported by assays measuring HIV-1 p24 antigen production in supernatants of 7- or 10-day cultures. DNA sequence analyses to identify mutations in the reverse transcriptase gene that cause resistance to 3'-azido-3'-deoxythymidine also support the PDQ results. With the PDQ method, both infectivity titration and susceptibility testing can be performed on supernatants from primary cultures of peripheral blood mononuclear cells. PDQ susceptibility testing should facilitate epidemiologic studies of the clinical significance of drug-resistant HIV-1 isolates.

IL-9 expression by human eosinophils: regulation by IL-1beta and TNF-alpha.

PubMed

Gounni, A S; Nutku, E; Koussih, L; Aris, F; Louahed, J; Levitt, R C; Nicolaides, N C; Hamid, Q

2000-09-01

IL-9 is a pleiotropic cytokine that exhibits biologic activity on cells of diverse hemopoietic lineage. IL-9 stimulates the proliferation of activated T cells, enhances the production of IgE from B cells, and promotes the proliferation and differentiation of mast cells and hematopoietic progenitors. In this study we evaluated the expression of IL-9 messenger (m)RNA and protein by human peripheral blood eosinophils. We also investigated the role of IL-1beta and TNF-alpha in the release of IL-9 from human peripheral blood eosinophils. RT-PCR, in situ hybridization, and immunocytochemistry were used to investigate the presence of IL-9 mRNA and protein in human peripheral blood eosinophils from asthmatic patients and normal control subjects. Furthermore, biologic assay was used to investigate the release of IL-9 protein from IL-1beta- or TNF-alpha-stimulated eosinophils in vitro. RT-PCR analysis showed the presence of IL-9 mRNA in human peripheral blood eosinophil RNA preparations from subjects with atopic asthma, as well as in the eosinophil-differentiated HL-60 cell line. By using in situ hybridization, a significant difference (P <.01) in IL-9 mRNA expression was detected in human peripheral blood eosinophils freshly isolated from asthmatic subjects compared with those isolated from normal control subjects. Furthermore, the percentage of IL-9 immunoreactive eosinophils from asthmatic patients was increased compared with that found in normal control subjects (P <.01). We also demonstrate that cultured human peripheral blood eosinophils from asthmatic subjects synthesize and release IL-9 protein, which is upregulated on stimulation with TNF-alpha and IL-1beta. Human eosinophils express biologically active IL-9, which suggests that these cells may influence the recruitment and activation of effector cells linked to the pathogenesis of allergic disease. These observations provide further evidence for the role of eosinophils in regulating airway immune responses.

[Influence of Cryopreservation on Human Peripheral Blood Mononuclear Cell Immunocompetence].

PubMed

Pan, Xue-Feng; Lu, Chun-Xia; Yang, Li-Li; Shu, Chang; Yao, Na; Zuo, Hong-Bin; Cui, Li-Feng

2016-08-01

To establish a method for isolation, cryopreservation and recovery of the highly viable human peripheral blood monomuclear cells (PBMNCs) so as to achieve the long-term preservation of PBMNCs. A total of 80-100 ml peripheral blood were collected from the healthy volumteers aged over 50 years old. The PBMNCs were isolated by the Ficoll density gradient technique and cryopreserved gradually by program control method in liquid nitrogen freezer of -196 °C. The serum-free medium and autoloqous plasma medium were test for preservation of PBMNCs. The cell viability was assessed at time point of 1, 2, 4, 8, 12 and 24 months after thawing. Finally, the proliferation ability, purity and cytotoxicity were compared between the autologous immune lymphocytes (AIL) induced from cryopreserved PBMNCs and AIL as control from fresh PBMNCs. After separating, the cell viability was 99.6%±0.4%, and the recovery rate of lymphocytes was 58.4%±6.52%. The cell recovery rate of lymphocyte was 89.7%±3.82% at 24 months. The quality assurance program was reliable within 2 years of running. The AIL cells induced with cryopreserved PBMNCs were not significantly different from those induced from fresh PBMNCs in terms of proliferative action, purity and cytotoxicity(CD3(+)CD8(+) ≥45%,CD3(+)CD56(+) NKT≥10%,CD4(+)CD25(+) NKT≤10%). Manual separation of lymphocytes in vitro can get enough high-quality PBMNCs. The long-term cryopreserved PBMNC still maintain their high viability. The reinfusion of the clinical autologous immune cells would be advantageous for early tumor immunotherapy. Human AIL induced from cryopreserved PBMNC maintain their anti-tumor ability. These findings have the important implications for the application of these cells to adoptive cellular therapy.

Relation between clinical mature and immature lymphocyte cells in human peripheral blood and their spatial label free scattering patterns

NASA Astrophysics Data System (ADS)

Zhang, Lu; Zhao, Xin; Zhang, Zhenxi; Zhao, Hong; Chen, Wei; Yuan, Li

2016-07-01

A single living cell's light scattering pattern (LSP) in the horizontal plane, which has been denoted as the cell's "2D fingerprint," may provide a powerful label-free detection tool in clinical applications. We have recently studied the LSP in spatial scattering planes, denoted as the cell's "3D fingerprint," for mature and immature lymphocyte cells in human peripheral blood. The effects of membrane size, morphology, and the existence of the nucleus on the spatial LSP are discussed. In order to distinguish clinical label-free mature and immature lymphocytes, the special features of the spatial LSP are studied by statistical method in both the spatial and frequency domains. Spatial LSP provides rich information on the cell's morphology and contents, which can distinguish mature from immature lymphocyte cells and hence ultimately it may be a useful label-free technique for clinical leukemia diagnosis.

Isolation of Human Skin Dendritic Cell Subsets.

PubMed

Gunawan, Merry; Jardine, Laura; Haniffa, Muzlifah

2016-01-01

Dendritic cells (DCs) are specialized leukocytes with antigen-processing and antigen-presenting functions. DCs can be divided into distinct subsets by anatomical location, phenotype and function. In human, the two most accessible tissues to study leukocytes are peripheral blood and skin. DCs are rare in human peripheral blood (<1 % of mononuclear cells) and have a less mature phenotype than their tissue counterparts (MacDonald et al., Blood. 100:4512-4520, 2002; Haniffa et al., Immunity 37:60-73, 2012). In contrast, the skin covering an average total surface area of 1.8 m(2) has approximately tenfold more DCs than the average 5 L of total blood volume (Wang et al., J Invest Dermatol 134:965-974, 2014). DCs migrate spontaneously from skin explants cultured ex vivo, which provide an easy method of cell isolation (Larsen et al., J Exp Med 172:1483-1493, 1990; Lenz et al., J Clin Invest 92:2587-2596, 1993; Nestle et al., J Immunol 151:6535-6545, 1993). These factors led to the extensive use of skin DCs as the "prototype" migratory DCs in human studies. In this chapter, we detail the protocols to isolate DCs and resident macrophages from human skin. We also provide a multiparameter flow cytometry gating strategy to identify human skin DCs and to distinguish them from macrophages.

Elucidation of Seventeen Human Peripheral Blood B cell Subsets and Quantification of the Tetanus Response Using a Density-Based Method for the Automated Identification of Cell Populations in Multidimensional Flow Cytometry Data

PubMed Central

Qian, Yu; Wei, Chungwen; Lee, F. Eun-Hyung; Campbell, John; Halliley, Jessica; Lee, Jamie A.; Cai, Jennifer; Kong, Megan; Sadat, Eva; Thomson, Elizabeth; Dunn, Patrick; Seegmiller, Adam C.; Karandikar, Nitin J.; Tipton, Chris; Mosmann, Tim; Sanz, Iñaki; Scheuermann, Richard H.

2011-01-01

Background Advances in multi-parameter flow cytometry (FCM) now allow for the independent detection of larger numbers of fluorochromes on individual cells, generating data with increasingly higher dimensionality. The increased complexity of these data has made it difficult to identify cell populations from high-dimensional FCM data using traditional manual gating strategies based on single-color or two-color displays. Methods To address this challenge, we developed a novel program, FLOCK (FLOw Clustering without K), that uses a density-based clustering approach to algorithmically identify biologically relevant cell populations from multiple samples in an unbiased fashion, thereby eliminating operator-dependent variability. Results FLOCK was used to objectively identify seventeen distinct B cell subsets in a human peripheral blood sample and to identify and quantify novel plasmablast subsets responding transiently to tetanus and other vaccinations in peripheral blood. FLOCK has been implemented in the publically available Immunology Database and Analysis Portal – ImmPort (http://www.immport.org) for open use by the immunology research community. Conclusions FLOCK is able to identify cell subsets in experiments that use multi-parameter flow cytometry through an objective, automated computational approach. The use of algorithms like FLOCK for FCM data analysis obviates the need for subjective and labor intensive manual gating to identify and quantify cell subsets. Novel populations identified by these computational approaches can serve as hypotheses for further experimental study. PMID:20839340

Rapid resetting of human peripheral clocks by phototherapy during simulated night shift work.

PubMed

Cuesta, Marc; Boudreau, Philippe; Cermakian, Nicolas; Boivin, Diane B

2017-11-24

A majority of night shift workers have their circadian rhythms misaligned to their atypical schedule. While bright light exposure at night is known to reset the human central circadian clock, the behavior of peripheral clocks under conditions of shift work is more elusive. The aim of the present study was to quantify the resetting effects of bright light exposure on both central (plasma cortisol and melatonin) and peripheral clocks markers (clock gene expression in peripheral blood mononuclear cells, PBMCs) in subjects living at night. Eighteen healthy subjects were enrolled to either a control (dim light) or a bright light group. Blood was sampled at baseline and on the 4 th day of simulated night shift. In response to a night-oriented schedule, the phase of PER1 and BMAL1 rhythms in PBMCs was delayed by ~2.5-3 h (P < 0.05), while no shift was observed for the other clock genes and the central markers. Three cycles of 8-h bright light induced significant phase delays (P < 0.05) of ~7-9 h for central and peripheral markers, except BMAL1 (advanced by +5h29; P < 0.05). Here, we demonstrate in humans a lack of peripheral clock adaptation under a night-oriented schedule and a rapid resetting effect of nocturnal bright light exposure on peripheral clocks.

[Inhibitory effect and mechanism of tofacitinib on the secretion of cytokines by T cells in human peripheral blood].

PubMed

Wu, Kunlun; Zhao, Jun; Wu, Qiongli; Wu, Changyou

2017-11-01

Objective To study the inhibitory effect of tofacitinib on the production of cytokines by T cells in human peripheral blood and its mechanism. Methods Peripheral blood mononuclear cells (PBMCs) and purified T cells were cultured and stimulated with anti-CD3 plus anti-CD28 antibodies in the presence or absence of tofacitinib (0.5 μmol/L). The levels of interferon γ (IFN-γ), tumor necrosis factor α (TNF-α) and interleukin 2 (IL-2) in the culture supernatants were detected by ELISA, and the expressions of activated molecules CD69 and CD25 on the surface of CD4 + and CD8 + T cells, the production of cytokines and the phosphorylation of signal transducers and transcriptional activators STAT1, STAT3, STAT4 in T cells were examined by flow cytometry. At the same time, the proliferation and apoptosis of T cells were observed by 5- (and 6-) carboxyfluorescein diacetate succinimidyl ester (CFSE) staining and the flow cy tometry with annexin V-FITC/PI, respectively. Results Tofacitinib inhibited the production of IFN-γ, TNF-α and the expression of CD25 on T cells from the peripheral blood. In addition, the proliferation and the phosphorylation of STAT1, STAT3, STAT4 by T cells were also depressed. However, tofacitinib had no effect on the secretion of IL-2, the expression of CD69 and the apoptosis of T cells. Conclusion Tofacitinib can inhibit the secretion of IFN-γ and TNF-α by T cells in the peripheral blood, and its mechanism might be related to the inhibitory effect of tofacitinib on the activation, proliferation and signal transduction in T cells.

The Prussian Academy of Sciences during the Third Reich

ERIC Educational Resources Information Center

Notzoldt, Peter; Walther, Peter Th.

2004-01-01

In 1933, the Prussian Academy of Sciences and Humanities was an exclusive learned society, out of touch with modern methods and funding, which had also failed to re-establish itself as a "centre of research". During the Nazi regime, it was at best peripherally involved in the restructuring of German academia. While some of its members…

Flow cytometric assay for analysis of cytotoxic effects of potential drugs on human peripheral blood leukocytes

NASA Astrophysics Data System (ADS)

Nieschke, Kathleen; Mittag, Anja; Golab, Karolina; Bocsi, Jozsef; Pierzchalski, Arkadiusz; Kamysz, Wojciech; Tarnok, Attila

2014-03-01

Toxicity test of new chemicals belongs to the first steps in the drug screening, using different cultured cell lines. However, primary human cells represent the human organism better than cultured tumor derived cell lines. We developed a very gentle toxicity assay for isolation and incubation of human peripheral blood leukocytes (PBL) and tested it using different bioactive oligopeptides (OP). Effects of different PBL isolation methods (red blood cell lysis; Histopaque isolation among others), different incubation tubes (e.g. FACS tubes), anticoagulants and blood sources on PBL viability were tested using propidium iodide-exclusion as viability measure (incubation time: 60 min, 36°C) and flow cytometry. Toxicity concentration and time-depended effects (10-60 min, 36 °C, 0-100 μg /ml of OP) on human PBL were analyzed. Erythrocyte lysis by hypotonic shock (dH2O) was the fastest PBL isolation method with highest viability (>85%) compared to NH4Cl-Lysis (49%). Density gradient centrifugation led to neutrophil granulocyte cell loss. Heparin anticoagulation resulted in higher viability than EDTA. Conical 1.5 mL and 2 mL micro-reaction tubes (both polypropylene (PP)) had the highest viability (99% and 97%) compared to other tubes, i.e. three types of 5.0 mL round-bottom tubes PP (opaque-60%), PP (blue-62%), Polystyrene (PS-64%). Viability of PBL did not differ between venous and capillary blood. A gentle reproducible preparation and analytical toxicity-assay for human PBL was developed and evaluated. Using our assay toxicity, time-course, dose-dependence and aggregate formation by OP could be clearly differentiated and quantified. This novel assay enables for rapid and cost effective multiparametric toxicological screening and pharmacological testing on primary human PBL and can be adapted to high-throughput-screening.°z

Physiologic Pressure and Flow Changes During Parabolic Flight (Pilot Study)

NASA Technical Reports Server (NTRS)

Pantalos, George; Sharp, M. Keith; Mathias, John R.; Hargens, Alan R.; Watenpaugh, Donald E.; Buckey, Jay C.

1999-01-01

The objective of this study was to obtain measurement of cutaneous tissue perfusion central and peripheral venous pressure, and esophageal and abdominal pressure in human test subjects during parabolic flight. Hemodynamic data recorded during SLS-I and SLS-2 missions have resulted in the paradoxical finding of increased cardiac stroke volume in the presence of a decreased central venous pressure (CVP) following entry in weightlessness. The investigators have proposed that in the absence of gravity, acceleration-induced peripheral vascular compression is relieved, increasing peripheral vascular capacity and flow while reducing central and peripheral venous pressure, This pilot study seeks to measure blood pressure and flow in human test subjects during parabolic flight for different postures.

Exposure to non-ionizing radiation provokes changes in rat thyroid morphology and expression of HSP-90

PubMed Central

Misa-Agustiño, Maria J; Jorge-Mora, Teresa; Jorge-Barreiro, Francisco J; Suarez-Quintanilla, Juan; Moreno-Piquero, Eduardo; Ares-Pena, Francisco J

2015-01-01

Non-ionizing radiation at 2.45 GHz may modify the morphology and expression of genes that codify heat shock proteins (HSP) in the thyroid gland. Diathermy is the therapeutic application of non-ionizing radiation to humans for its beneficial effects in rheumatological and musculo-skeletal pain processes. We used a diathermy model on laboratory rats subjected to maximum exposure in the left front leg, in order to study the effects of radiation on the nearby thyroid tissue. Fifty-six rats were individually exposed once or repeatedly (10 times in two weeks) for 30 min to 2.45 GHz radiation in a commercial chamber at different non-thermal specific absorption rates (SARs), which were calculated using the finite difference time domain technique. We used immunohistochemistry methods to study the expression of HSP-90 and morphological changes in thyroid gland tissues. Ninety minutes after radiation with the highest SAR, the central and peripheral follicles presented increased size and the thickness of the peripheral septa had decreased. Twenty-four hours after radiation, only peripheral follicles radiated at 12 W were found to be smaller. Peripheral follicles increased in size with repeated exposure at 3 W power. Morphological changes in the thyroid tissue may indicate a glandular response to acute or repeated stress from radiation in the hypothalamic–pituitary–thyroid axis. Further research is needed to determine if the effect of this physical agent over time may cause disease in the human thyroid gland. PMID:25649190

Systems and methods to control multiple peripherals with a single-peripheral application code

DOEpatents

Ransom, Ray M.

2013-06-11

Methods and apparatus are provided for enhancing the BIOS of a hardware peripheral device to manage multiple peripheral devices simultaneously without modifying the application software of the peripheral device. The apparatus comprises a logic control unit and a memory in communication with the logic control unit. The memory is partitioned into a plurality of ranges, each range comprising one or more blocks of memory, one range being associated with each instance of the peripheral application and one range being reserved for storage of a data pointer related to each peripheral application of the plurality. The logic control unit is configured to operate multiple instances of the control application by duplicating one instance of the peripheral application for each peripheral device of the plurality and partitioning a memory device into partitions comprising one or more blocks of memory, one partition being associated with each instance of the peripheral application. The method then reserves a range of memory addresses for storage of a data pointer related to each peripheral device of the plurality, and initializes each of the plurality of peripheral devices.

Explicit formula of finite difference method to estimate human peripheral tissue temperatures during exposure to severe cold stress.

PubMed

Khanday, M A; Hussain, Fida

2015-02-01

During cold exposure, peripheral tissues undergo vasoconstriction to minimize heat loss to preserve the maintenance of a normal core temperature. However, vasoconstricted tissues exposed to cold temperatures are susceptible to freezing and frostbite-related tissue damage. Therefore, it is imperative to establish a mathematical model for the estimation of tissue necrosis due to cold stress. To this end, an explicit formula of finite difference method has been used to obtain the solution of Pennes' bio-heat equation with appropriate boundary conditions to estimate the temperature profiles of dermal and subdermal layers when exposed to severe cold temperatures. The discrete values of nodal temperature were calculated at the interfaces of skin and subcutaneous tissues with respect to the atmospheric temperatures of 25 °C, 20 °C, 15 °C, 5 °C, -5 °C and -10 °C. The results obtained were used to identify the scenarios under which various degrees of frostbite occur on the surface of skin as well as the dermal and subdermal areas. The explicit formula of finite difference method proposed in this model provides more accurate predictions as compared to other numerical methods. This model of predicting tissue temperatures provides researchers with a more accurate prediction of peripheral tissue temperature and, hence, the susceptibility to frostbite during severe cold exposure. Copyright © 2014 Elsevier Ltd. All rights reserved.

Lack of oblique astigmatism in the chicken eye.

PubMed

Maier, Felix M; Howland, Howard C; Ohlendorf, Arne; Wahl, Siegfried; Schaeffel, Frank

2015-04-01

Primate eyes display considerable oblique off-axis astigmatism which could provide information on the sign of defocus that is needed for emmetropization. The pattern of peripheral astigmatism is not known in the chicken eye, a common model of myopia. Peripheral astigmatism was mapped out over the horizontal visual field in three chickens, 43 days old, and in three near emmetropic human subjects, average age 34.7years, using infrared photoretinoscopy. There were no differences in astigmatism between humans and chickens in the central visual field (chicks -0.35D, humans -0.65D, n.s.) but large differences in the periphery (i.e. astigmatism at 40° in the temporal visual field: humans -4.21D, chicks -0.63D, p<0.001, unpaired t-test). The lack of peripheral astigmatism in chicks was not due to differences in corneal shape. Perhaps related to their superior peripheral optics, we found that chickens had excellent visual performance also in the far periphery. Using an automated optokinetic nystagmus paradigm, no difference was observed in spatial visual performance with vision restricted to either the central 67° of the visual field or to the periphery beyond 67°. Accommodation was elicited by stimuli presented far out in the visual field. Transscleral images of single infrared LEDs showed no sign of peripheral astigmatism. The chick may be the first terrestrial vertebrate described to lack oblique astigmatism. Since corneal shape cannot account for the difference in astigmatism in humans and chicks, it must trace back to the design of the crystalline lens. The lack of peripheral astigmatism in chicks also excludes a role in emmetropization. Copyright © 2015 Elsevier Ltd. All rights reserved.

A novel method for evaluating antibody-dependent cell-mediated cytotoxicity by flowcytometry using cryopreserved human peripheral blood mononuclear cells

PubMed Central

Yamashita, Makiko; Kitano, Shigehisa; Aikawa, Hiroaki; Kuchiba, Aya; Hayashi, Mitsuhiro; Yamamoto, Noboru; Tamura, Kenji; Hamada, Akinobu

2016-01-01

Analyzing the cytotoxic functions of effector cells, such as NK cells against target cancer cells, is thought to be necessary for predicting the clinical efficacy of antibody-dependent cellular cytotoxicity (ADCC) -dependent antibody therapy. The 51Cr release assay has long been the most widely used method for quantification of ADCC activity. However, the reproducibilities of these release assays are not adequate, and they do not allow evaluation of the lysis susceptibilities of distinct cell types within the target cell population. In this study, we established a novel method for evaluating cytotoxicity, which involves the detection and quantification of dead target cells using flowcytometry. CFSE (carboxyfluorescein succinimidyl ester) was used as a dye to specifically stain and thereby label the target cell population, allowing living and dead cells, as well as both target and effector cells, to be quantitatively distinguished. Furthermore, with our new approach, ADCC activity was more reproducibly, sensitively, and specifically detectable, not only in freshly isolated but also in frozen human peripheral blood mononuclear cells (PBMCs), than with the calcein-AM release assay. This assay, validated herein, is expected to become a standard assay for evaluating ADCC activity which will ultimately contribute the clinical development of ADCC dependent-antibody therapies. PMID:26813960

A novel method for evaluating antibody-dependent cell-mediated cytotoxicity by flowcytometry using cryopreserved human peripheral blood mononuclear cells.

PubMed

Yamashita, Makiko; Kitano, Shigehisa; Aikawa, Hiroaki; Kuchiba, Aya; Hayashi, Mitsuhiro; Yamamoto, Noboru; Tamura, Kenji; Hamada, Akinobu

2016-01-27

Analyzing the cytotoxic functions of effector cells, such as NK cells against target cancer cells, is thought to be necessary for predicting the clinical efficacy of antibody-dependent cellular cytotoxicity (ADCC) -dependent antibody therapy. The (51)Cr release assay has long been the most widely used method for quantification of ADCC activity. However, the reproducibilities of these release assays are not adequate, and they do not allow evaluation of the lysis susceptibilities of distinct cell types within the target cell population. In this study, we established a novel method for evaluating cytotoxicity, which involves the detection and quantification of dead target cells using flowcytometry. CFSE (carboxyfluorescein succinimidyl ester) was used as a dye to specifically stain and thereby label the target cell population, allowing living and dead cells, as well as both target and effector cells, to be quantitatively distinguished. Furthermore, with our new approach, ADCC activity was more reproducibly, sensitively, and specifically detectable, not only in freshly isolated but also in frozen human peripheral blood mononuclear cells (PBMCs), than with the calcein-AM release assay. This assay, validated herein, is expected to become a standard assay for evaluating ADCC activity which will ultimately contribute the clinical development of ADCC dependent-antibody therapies.

Time-resolved fluorescence monitoring of cholesterol in peripheral blood mononuclear cells

NASA Astrophysics Data System (ADS)

Martinakova, Z.; Horilova, J.; Lajdova, I.; Marcek Chorvatova, A.

2014-12-01

Precise evaluation of intracellular cholesterol distribution is crucial for improving diagnostics of diseased states associated with cholesterol alteration. Time-resolved fluorescence techniques are tested for non-invasive investigation of cholesterol in living cells. Fluorescent probe NBD attached to cholesterol was employed to evaluate cholesterol distribution in peripheral blood mononuclear cells (PBMC) isolated from the human blood. Fluorescence Lifetime Imaging Microscopy (FLIM) was successfully applied to simultaneously monitor the spatial distribution and the timeresolved characteristics of the NBD-cholesterol fluorescence in PBMC. Gathered data are the first step in the development of a new perspective non-invasive diagnostic method for evaluation of cholesterol modifications in diseases associated with disorders of lipid metabolism.

Influence of Vancomycin Infusion Methods on Endothelial Cell Toxicity

PubMed Central

Drouet, Maryline; Chai, Feng; Barthélémy, Christine; Lebuffe, Gilles; Debaene, Bertrand; Odou, Pascal

2014-01-01

Peripheral intravenous therapy is frequently used in routine hospital practice and, due to various factors, its most common side effect is phlebitis. The infusion of vancomycin is particularly associated with phlebitis despite its widespread use. French guidelines recommend central intravenous infusion for high concentrations of vancomycin, but peripheral intravenous therapy is often preferred in intensive care units. Methods of vancomycin infusion are either intermittent infusion or continuous infusion. A comparison of these methods under in vitro conditions simulating clinical use could result in better infusion efficacy. Human umbilical vein endothelial cells (HUVECs) were therefore challenged with clinical doses of vancomycin over a 24- to 72-h period using these infusion methods. Cell death was measured with the alamarBlue test. Concentration-dependent and time-dependent vancomycin toxicity on HUVECs was noted with a 50% lethal dose at 5 mg/ml after 24 h, reaching 2.5 mg/ml after 72 h of infusion, simulating long-term infusion. This toxicity does not seem to be induced by acidic pH. In comparing infusion methods, we observed that continuous infusion induced greater cell toxicity than intermittent infusion at doses higher than 1 g/day. The increasing use of vancomycin means that new guidelines are required to avoid phlebitis. If peripheral intravenous therapy is used to reduce infusion time, along with intermittent infusion, vein irritation and localized phlebitis may be reduced. Further studies have to be carried out to explore the causes of vancomycin endothelial toxicity. PMID:25421476

Forensic differentiation between peripheral and menstrual blood in cases of alleged sexual assault-validating an immunochromatographic multiplex assay for simultaneous detection of human hemoglobin and D-dimer.

PubMed

Holtkötter, Hannah; Dias Filho, Claudemir Rodrigues; Schwender, Kristina; Stadler, Christian; Vennemann, Marielle; Pacheco, Ana Claudia; Roca, Gabriela

2018-05-01

Sexual assault is a serious offense and identification of body fluids originating from sexual activity has been a crucial aspect of forensic investigations for a long time. While reliable tests for the detection of semen and saliva have been successfully implemented into forensic laboratories, the detection of other body fluids, such as vaginal or menstrual fluid, is more challenging. Especially, the discrimination between peripheral and menstrual blood can be highly relevant for police investigations because it provides potential evidence regarding the issue of consent. We report the forensic validation of an immunochromatographic test that allows for such discrimination in forensic stains, the SERATEC PMB test, and its performance on real casework samples. The PMB test is a duplex test combining human hemoglobin and D-dimer detection and was developed for the identification of blood and menstrual fluid, both at the crime scene and in the laboratory. The results of this study showed that the duplex D-dimer/hemoglobin assay reliably detects the presence of human hemoglobin and identifies samples containing menstrual fluid by detecting the presence of D-dimers. The method distinguished between menstrual and peripheral blood in a swab from a historical artifact and in real casework samples of alleged sexual assaults. Results show that the development of the new duplex test is a substantial progress towards analyzing and interpreting evidence from sexual assault cases.

76 FR 44595 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug... Committee: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee...

Amyloid-β efflux from the CNS into the plasma

PubMed Central

Roberts, Kaleigh Filisa; Elbert, Donald L.; Kasten, Tom P.; Patterson, Bruce W.; Sigurdson, Wendy C.; Connors, Rose E.; Ovod, Vitaliy; Munsell, Ling Y.; Mawuenyega, Kwasi G.; Miller-Thomas, Michelle M.; Moran, Christopher J.; Cross, Dewitte T.; Derdeyn, Colin P.; Bateman, Randall J.

2015-01-01

Objective The aim of this study was to measure the flux of amyloid-β (Aβ) across the human cerebral capillary bed in order to determine if transport into the blood is a significant mechanism of clearance for Aβ produced in the central nervous system (CNS). Methods Time-matched blood samples were simultaneously collected from a cerebral vein (including the sigmoid sinus, inferior petrosal sinus, and the internal jugular vein), femoral vein, and radial artery of patients undergoing Inferior Petrosal Sinus Sampling (IPSS). For each plasma sample, Aβ concentration was assessed by three assays and the venous to arterial Aβ concentration ratios were determined. Results Aβ concentration was increased by ~7.5% in venous blood leaving the CNS capillary bed compared to arterial blood, indicating efflux from the CNS into the peripheral blood (p < 0.0001). There was no difference in peripheral venous Aβ concentration compared to arterial blood concentration. Interpretation Our results are consistent with clearance of CNS-derived Aβ into the venous blood supply with no increase from a peripheral capillary bed. Modeling these results suggests that direct transport of Aβ across the blood-brain barrier accounts for ~25% of Aβ clearance, and reabsorption of cerebrospinal fluid Aβ accounts for ~25% of the total CNS Aβ clearance in humans. PMID:25205593

Anti-thymocyte globulin as graft-versus-host disease prevention in the setting of allogeneic peripheral blood stem cell transplantation: a review from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

PubMed Central

Baron, Frédéric; Mohty, Mohamad; Blaise, Didier; Socié, Gérard; Labopin, Myriam; Esteve, Jordi; Ciceri, Fabio; Giebel, Sebastian; Gorin, Norbert Claude; Savani, Bipin N; Schmid, Christoph; Nagler, Arnon

2017-01-01

Allogeneic hematopoietic stem cell transplantation is increasingly used as treatment for patients with life-threatening blood diseases. Its curative potential is largely based on immune-mediated graft-versus-leukemia effects caused by donor T cells contained in the graft. Unfortunately, donor T cells are also the cause of graft-versus-host disease. The vast majority of human leukocyte antigen-matched allogeneic hematopoietic stem cell transplants are nowadays carried out with peripheral blood stem cells as the stem cell source. In comparison with bone marrows, peripheral blood stem cells contain more hematopoietic stem/progenitor cells but also one log more T cells. Consequently, the use of peripheral blood stem cells instead of bone marrow has been associated with faster hematologic recovery and a lower risk of relapse in patients with advanced disease, but also with a higher incidence of chronic graft-versus-host disease. These observations have been the basis for several studies aimed at assessing the impact of immunoregulation with anti-thymocyte globulin on transplantation outcomes in patients given human leukocyte antigen-matched peripheral blood stem cells from related or unrelated donors. After a brief introduction on anti-thymocyte globulin, this article reviews recent studies assessing the impact of anti-thymocyte globulin on transplantation outcomes in patients given peripheral blood stem cells from human leukocyte antigen-matched related or unrelated donors as well as in recipients of grafts from human leukocyte antigen haploidentical donors. PMID:27927772

Attentional load and sensory competition in human vision: modulation of fMRI responses by load at fixation during task-irrelevant stimulation in the peripheral visual field.

PubMed

Schwartz, Sophie; Vuilleumier, Patrik; Hutton, Chloe; Maravita, Angelo; Dolan, Raymond J; Driver, Jon

2005-06-01

Perceptual suppression of distractors may depend on both endogenous and exogenous factors, such as attentional load of the current task and sensory competition among simultaneous stimuli, respectively. We used functional magnetic resonance imaging (fMRI) to compare these two types of attentional effects and examine how they may interact in the human brain. We varied the attentional load of a visual monitoring task performed on a rapid stream at central fixation without altering the central stimuli themselves, while measuring the impact on fMRI responses to task-irrelevant peripheral checkerboards presented either unilaterally or bilaterally. Activations in visual cortex for irrelevant peripheral stimulation decreased with increasing attentional load at fixation. This relative decrease was present even in V1, but became larger for successive visual areas through to V4. Decreases in activation for contralateral peripheral checkerboards due to higher central load were more pronounced within retinotopic cortex corresponding to 'inner' peripheral locations relatively near the central targets than for more eccentric 'outer' locations, demonstrating a predominant suppression of nearby surround rather than strict 'tunnel vision' during higher task load at central fixation. Contralateral activations for peripheral stimulation in one hemifield were reduced by competition with concurrent stimulation in the other hemifield only in inferior parietal cortex, not in retinotopic areas of occipital visual cortex. In addition, central attentional load interacted with competition due to bilateral versus unilateral peripheral stimuli specifically in posterior parietal and fusiform regions. These results reveal that task-dependent attentional load, and interhemifield stimulus-competition, can produce distinct influences on the neural responses to peripheral visual stimuli within the human visual system. These distinct mechanisms in selective visual processing may be integrated within posterior parietal areas, rather than earlier occipital cortex.

Herpes virus infection of the peripheral nervous system.

PubMed

Steiner, Israel

2013-01-01

Among the human herpes viruses, three are neurotropic and capable of producing severe neurological abnormalities: herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) and varicella-zoster virus (VZV). Both the acute, primary infection and the reactivation from the site of latent infection, the dorsal sensory ganglia, are associated with severe human morbidity and mortality. The peripheral nervous system is one of the major loci affected by these viruses. The present review details the virology and molecular biology underlying the human infection. This is followed by detailed description of the symtomatology, clinical presentation, diagnosis, course, therapy, and prognosis of disorders of the peripheral nervous system caused by these viruses. Copyright © 2013 Elsevier B.V. All rights reserved.

Damage of chromosoms under irradiation of human blood lymphocytes and development of bystander effect.

PubMed

Shemetun, O V

2016-12-01

the research the distribution of radiation induced damages among chromosomes and their bands in irra diated in vitro human blood lymphocytes and in unirradiated bystander cells.Material and methods of research: cultivation of human peripheral blood lymphocytes by semi micromethod D.A. Hungerford, modeling of radiation induced bystander effect in mixed cultures consisting of irradiated in vitro and non irradiated blood lymphocytes from persons of different gender, GTG staining of metaphase chromosomes and their cytogenetic analysis. Break points in chromosomes under the formation of aberrations were identified in exposed in vitro human peripheral blood lymphocytes in doses 0.25 Gy (95 breaks in 1248 cells) and 1.0 Gy (227 breaks in 726 cells) and in non irradiated bystander cells under their joint cultivation with irradiated in vitro human lymphocytes (51 breaks in 1137 cells at irradiation of adjacent populations of lymphocytes in dose 0.25 Gy and 75 breaks in 1321 cells at irradiation of adjacent population of lymphocytes in a dose 1.0 Gy). The distribution of injuries among the chromo somes and their bands was investigated. in radiation exposed in vitro human peripheral blood lymphocytes as well as in bystander cells the fre quency of damaged bands and number of breaks which localized in them exceeded the control value (p < 0.01). As under direct radiation exposure, as under formation of breaks due to induction of bystander effect, chromosomes were damaged according to their relative length. Location of bands with increasing number of breaks coincided with the «hot spots» of chromosome damage following irradiation and fragile sites. More sensitive to damage were G negative euchromatin chromosome bands, in which were localized 82 88 % breaks. Damageability of telomeric regions in the irradiated cells had no significant difference from the control, while in bystander cells was lower than control value (p < 0.05). O. V. Shemetun.

Evaluation of Central and Peripheral Fatigue in the Quadriceps Using Fractal Dimension and Conduction Velocity in Young Females

PubMed Central

Beretta-Piccoli, Matteo; D’Antona, Giuseppe; Barbero, Marco; Fisher, Beth; Dieli-Conwright, Christina M.; Clijsen, Ron; Cescon, Corrado

2015-01-01

Purpose Over the past decade, linear and non-linear surface electromyography descriptors for central and peripheral components of fatigue have been developed. In the current study, we tested fractal dimension (FD) and conduction velocity (CV) as myoelectric descriptors of central and peripheral fatigue, respectively. To this aim, we analyzed FD and CV slopes during sustained fatiguing contractions of the quadriceps femoris in healthy humans. Methods A total of 29 recreationally active women (mean age±standard deviation: 24±4 years) and two female elite athletes (one power athlete, age 24 and one endurance athlete, age 30 years) performed two knee extensions: (1) at 20% maximal voluntary contraction (MVC) for 30 s, and (2) at 60% MVC held until exhaustion. Surface EMG signals were detected from the vastus lateralis and vastus medialis using bidimensional arrays. Results Central and peripheral fatigue were described as decreases in FD and CV, respectively. A positive correlation between FD and CV (R=0.51, p<0.01) was found during the sustained 60% MVC, probably as a result of simultaneous motor unit synchronization and a decrease in muscle fiber CV during the fatiguing task. Conclusions Central and peripheral fatigue can be described as changes in FD and CV, at least in young, healthy women. The significant correlation between FD and CV observed at 60% MVC suggests that a mutual interaction between central and peripheral fatigue can arise during submaximal isometric contractions. PMID:25880369

75 FR 17417 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

78 FR 63478 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

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2013-10-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

75 FR 36428 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

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2010-06-25

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

77 FR 20037 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

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2012-04-03

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

78 FR 63481 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

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2013-10-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

76 FR 3912 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

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2011-01-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

75 FR 12768 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

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2010-03-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

Effect of direct-fed microbial supplementation on the presence of Salmonella enterica in bovine peripheral lymph nodes

USDA-ARS?s Scientific Manuscript database

Introduction: Bovine peripheral lymph nodes (LN) contained within adipose trim, have been identified as a potential source of human exposure to Salmonella enterica, when incorporated into ground beef. How Salmonella gain entry to peripheral LN is a question yet to be answered, however recent survey...

[Pain in humans: experimental facts and hypotheses].

PubMed

Cesaro, P

1994-09-15

The description of painful phenomena in humans has to take into account its different components: sensory component (relevant to nociception), affective and emotional components. Nociceptor's (physiology is best understood with electrophysiological and neurochemical methods allowing a clear description of hyperalgesia, with its peripheral and spinal mechanisms. A functional model is partly available to explain allodynia, spontaneous burning pain and lightning pain, the three main consequences following deafferentation. At the thalamo-cortical level, one can describe nociceptive pathways and other pathways or neuronal networks involved in the affective and emotional components of pain.

Heat Tolerance and the Peripheral Effects of Anticholinergics. 1. A Non-Invasive Method for Estimating the Cholinergic Sensitivity of the Eccrine Glands in Humans.

DTIC Science & Technology

1985-01-30

exercise history for future data segregation. All tests were performed in an air-conditioned laboratory with subjects in a thermally neutral state. RESULTS ...UNCLASSIIED K K KRANING ET AL 38 AN 85 F/G 6/15 ImmonIIIIlIIfIIIIII wI L_- pu 1 .21. o 136 - MICROCOPY RESOLUTION TEST CHART NAT WOL. BUREAU OF...used as sensitive index of anticholiinergic drug potency. Independently, we developed 1 human sweat gland assayd d+ fftf -ng from theirs in several

Segregation of human peripheral blood lymphocytes according to their affinity for insolubilized histamine. Principal differences between males and females.

PubMed Central

Tartakovsky, B; Segal, S; Shani, A; Hellerstein, S; Weinstein, Y; Bentwich, Z

1979-01-01

An attempt was made to investigate the possible existence of differences in the composition of peripheral blood lymphocytes between males and females. Using affinity chromatography of human peripheral mononuclear cells on insolubilized histamine together with staining by fluoresceinated histamine-rabbit serum albumin (HRSA) we revealed that males possess a significantly higher proportion of mononuclear cells which bind to HRSA. These results are also reflected in sex-related differences in proliferative responses of the HRSA-non-adherent mononuclear cell population to T cell-dependent mitogens antigens and allogeneic mononuclear cells. PMID:160849

Ex Vivo Expanded Human Regulatory T Cells Can Prolong Survival of a Human Islet Allograft in a Humanized Mouse Model

PubMed Central

Wu, Douglas C.; Hester, Joanna; Nadig, Satish N.; Zhang, Wei; Trzonkowski, Piotr; Gray, Derek; Hughes, Stephen; Johnson, Paul; Wood, Kathryn J.

2013-01-01

Background Human regulatory T cells (Treg) offer an attractive adjunctive therapy to reduce current reliance on lifelong, nonspecific immunosuppression after transplantation. Here, we evaluated the ability of ex vivo expanded human Treg to prevent the rejection of islets of Langerhans in a humanized mouse model and examined the mechanisms involved. Methods We engrafted human pancreatic islets of Langerhans into the renal subcapsular space of immunodeficient BALB/c.rag2−/−.cγ−/− mice, previously rendered diabetic via injection of the β-cell toxin streptozocin. After the establishment of stable euglycemia, mice were reconstituted with allogeneic human peripheral blood mononuclear cells (PBMC) and the resultant alloreactive response studied. Ex vivo expanded CD25highCD4+ human Treg, which expressed FoxP3, CTLA-4, and CD62L and remained CD127low, were then cotransferred together with human PBMC and islet allografts and monitored for evidence of rejection. Results Human islets transplanted into diabetic immunodeficient mice reversed diabetes but were rejected rapidly after the mice were reconstituted with allogeneic human PBMC. Cotransfer of purified, ex vivo expanded human Treg prolonged islet allograft survival resulting in the accumulation of Treg in the peripheral lymphoid tissue and suppression of proliferation and interferon-γ production by T cells. In vitro, Treg suppressed activation of signal transducers and activators of transcription and inhibited the effector differentiation of responder T cells. Conclusions Ex vivo expanded Treg retain regulatory activity in vivo, can protect a human islet allograft from rejection by suppressing signal transducers and activators of transcription activation and inhibiting T-cell differentiation, and have clinical potential as an adjunctive cellular therapy. PMID:23917725

Relative peripheral hyperopic defocus alters central refractive development in infant monkeys

PubMed Central

Smith, Earl L.; Hung, Li-Fang; Huang, Juan

2009-01-01

Understanding the role of peripheral defocus on central refractive development is critical because refractive errors can vary significantly with eccentricity and peripheral refractions have been implicated in the genesis of central refractive errors in humans. Two rearing strategies were used to determine whether peripheral hyperopia alters central refractive development in rhesus monkeys. In intact eyes, lens-induced relative peripheral hyperopia produced central axial myopia. Moreover, eliminating the fovea by laser photoablation did not prevent compensating myopic changes in response to optically imposed hyperopia. These results show that peripheral refractive errors can have a substantial impact on central refractive development in primates. PMID:19632261

78 FR 60810 - Change to the Definition of “Human Organ” Under Section 301 of the National Organ Transplant Act...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-02

... hematopoietic stem cells (HSCs) within peripheral blood in the definition of ``bone marrow.'' This would clarify... of whether they were recovered directly from bone marrow (by aspiration) or from peripheral blood (by... consideration.'' ``Human organ'' is defined to include ``bone marrow * * * or any subpart thereof'' or any organ...

Large Extremity Peripheral Nerve Repair

DTIC Science & Technology

2013-10-01

show that the PTB method can provide fixation strengths approaching that of conventional microsurgery and that the PTB repair is unlikely to be...biomaterial during long periods of recovery associated with large nerve deficit reconstruction and long nerve grafts. As with the human amnion nerve...functional recovery model (SFI, sciatic function index) using PTB/xHAM wrap compared to standard (suture) of care microsurgery . Demonstrated improved nerve

Foveal analysis and peripheral selection during active visual sampling

PubMed Central

Ludwig, Casimir J. H.; Davies, J. Rhys; Eckstein, Miguel P.

2014-01-01

Human vision is an active process in which information is sampled during brief periods of stable fixation in between gaze shifts. Foveal analysis serves to identify the currently fixated object and has to be coordinated with a peripheral selection process of the next fixation location. Models of visual search and scene perception typically focus on the latter, without considering foveal processing requirements. We developed a dual-task noise classification technique that enables identification of the information uptake for foveal analysis and peripheral selection within a single fixation. Human observers had to use foveal vision to extract visual feature information (orientation) from different locations for a psychophysical comparison. The selection of to-be-fixated locations was guided by a different feature (luminance contrast). We inserted noise in both visual features and identified the uptake of information by looking at correlations between the noise at different points in time and behavior. Our data show that foveal analysis and peripheral selection proceeded completely in parallel. Peripheral processing stopped some time before the onset of an eye movement, but foveal analysis continued during this period. Variations in the difficulty of foveal processing did not influence the uptake of peripheral information and the efficacy of peripheral selection, suggesting that foveal analysis and peripheral selection operated independently. These results provide important theoretical constraints on how to model target selection in conjunction with foveal object identification: in parallel and independently. PMID:24385588

An alternative method for cDNA cloning from surrogate eukaryotic cells transfected with the corresponding genomic DNA.

PubMed

Hu, Lin-Yong; Cui, Chen-Chen; Song, Yu-Jie; Wang, Xiang-Guo; Jin, Ya-Ping; Wang, Ai-Hua; Zhang, Yong

2012-07-01

cDNA is widely used in gene function elucidation and/or transgenics research but often suitable tissues or cells from which to isolate mRNA for reverse transcription are unavailable. Here, an alternative method for cDNA cloning is described and tested by cloning the cDNA of human LALBA (human alpha-lactalbumin) from genomic DNA. First, genomic DNA containing all of the coding exons was cloned from human peripheral blood and inserted into a eukaryotic expression vector. Next, by delivering the plasmids into either 293T or fibroblast cells, surrogate cells were constructed. Finally, the total RNA was extracted from the surrogate cells and cDNA was obtained by RT-PCR. The human LALBA cDNA that was obtained was compared with the corresponding mRNA published in GenBank. The comparison showed that the two sequences were identical. The novel method for cDNA cloning from surrogate eukaryotic cells described here uses well-established techniques that are feasible and simple to use. We anticipate that this alternative method will have widespread applications.

Thyroxine differentially modulates the peripheral clock: lessons from the human hair follicle.

PubMed

Hardman, Jonathan A; Haslam, Iain S; Farjo, Nilofer; Farjo, Bessam; Paus, Ralf

2015-01-01

The human hair follicle (HF) exhibits peripheral clock activity, with knock-down of clock genes (BMAL1 and PER1) prolonging active hair growth (anagen) and increasing pigmentation. Similarly, thyroid hormones prolong anagen and stimulate pigmentation in cultured human HFs. In addition they are recognized as key regulators of the central clock that controls circadian rhythmicity. Therefore, we asked whether thyroxine (T4) also influences peripheral clock activity in the human HF. Over 24 hours we found a significant reduction in protein levels of BMAL1 and PER1, with their transcript levels also decreasing significantly. Furthermore, while all clock genes maintained their rhythmicity in both the control and T4 treated HFs, there was a significant reduction in the amplitude of BMAL1 and PER1 in T4 (100 nM) treated HFs. Accompanying this, cell-cycle progression marker Cyclin D1 was also assessed appearing to show an induced circadian rhythmicity by T4 however, this was not significant. Contrary to short term cultures, after 6 days, transcript and/or protein levels of all core clock genes (BMAL1, PER1, clock, CRY1, CRY2) were up-regulated in T4 treated HFs. BMAL1 and PER1 mRNA was also up-regulated in the HF bulge, the location of HF epithelial stem cells. Together this provides the first direct evidence that T4 modulates the expression of the peripheral molecular clock. Thus, patients with thyroid dysfunction may also show a disordered peripheral clock, which raises the possibility that short term, pulsatile treatment with T4 might permit one to modulate circadian activity in peripheral tissues as a target to treat clock-related disease.

The 78 kDa glucose-regulated protein (GRP78/BIP) is expressed on the cell membrane, is released into cell culture medium and is also present in human peripheral circulation.

PubMed

Delpino, Andrea; Castelli, Mauro

2002-01-01

In human rabdomiosarcoma cells (TE671/RD) chronic exposure to 500 nM thapsigargin (a powerful inhibitor of the endoplasmic reticulum Ca2+-ATPases) resulted in the induction of the stress protein GRP78/BIP. Making use of the surface biotinylation method, followed by the isolation of the GRP78 using ATP-agarose affinity chromatography, it was found that a fraction of the thapsigargin-induced GRP78 is expressed on the cell surface. The presence of GRP78 on the membrane of thapsigargin-treated cells was confirmed by fractionation of cell lysates into a soluble and a membrane fraction, followed by Western blot analysis with an anti-GRP78 antibody. It was also found that conspicuous amounts of GRP78 are present in the culture medium collected from thapsigargin-treated cultures. This extracellular GRP78 originates mostly by an active release from intact cells and does not result solely from the leakage of proteins from dead cells. Moreover, small amounts of circulating, free GRP78 and naturally-occurring anti-GRP78 autoantibodies were detected in the peripheral circulation of healthy human individuals.

Effects of intrathecal ketorolac on human experimental pain

PubMed Central

Eisenach, James C.; Curry, Regina; Tong, Chuanyao; Houle, Timothy T.; Yaksh, Tony L.

2010-01-01

Background Nonsteroidal antiinflammatory drugs, the most commonly used analgesics, reduce pain by inhibiting cyclooxygenase at peripheral sites of inflammation, but potentially also by inhibiting cyclooxygenase in the central nervous system, especially the spinal cord. Animal studies suggest that products of cyclooxygenase in the spinal cord do not alter pain responses to acute noxious stimuli, but reduce pain and sensitization following peripheral inflammation. We used spinal injection of small doses of the cyclooxygenase inhibitor, ketorolac, to survey the role of spinal cyclooxygenase in human experimental pain and hypersensitivity states. Methods Following regulatory agency approval and informed consent, we examined the effect of 2.0 mg intrathecal ketorolac in 41 healthy volunteers to acute noxious thermal stimuli in normal skin and to mechanical stimuli in skin sensitized by topical capsaicin or ultraviolet burn. We also examined the effect of intravenous ketorolac, Results Intrathecal ketorolac reduced hypersensitivity when it was induced by a combination of ultraviolet burn plus intermittent heat and, according to one of two analytical strategies, when it was induced by ultraviolet burn alone. Conclusions These data suggest a more limited role for spinal cord cyclooxygenase in human pain states than predicted by studies in animals. PMID:20395821

Child Maltreatment Is Associated with a Reduction of the Oxytocin Receptor in Peripheral Blood Mononuclear Cells

PubMed Central

Krause, Sabrina; Boeck, Christina; Gumpp, Anja M.; Rottler, Edit; Schury, Katharina; Karabatsiakis, Alexander; Buchheim, Anna; Gündel, Harald; Kolassa, Iris-Tatjana; Waller, Christiane

2018-01-01

Background: Child maltreatment (CM) and attachment experiences are closely linked to alterations in the human oxytocin (OXT) system. However, human data about oxytocin receptor (OXTR) protein levels are lacking. Therefore, we investigated oxytocin receptor (OXTR) protein levels in circulating immune cells and related them to circulating levels of OXT in peripheral blood. We hypothesized reduced OXTR protein levels, associated with both, experiences of CM and an insecure attachment representation. Methods: OXTR protein expressions were analyzed by western blot analyses in peripheral blood mononuclear cells (PBMC) and plasma OXT levels were determined by radioimmunoassay (RIA) in 49 mothers. We used the Childhood Trauma Questionnaire (CTQ) to assess adverse childhood experiences. Attachment representations (secure vs. insecure) were classified using the Adult Attachment Projective Picture System (AAP) and levels of anxiety and depression were assessed with the German version of the Hospital Depression and Anxiety scale (HADS-D). Results: CM-affected women showed significantly lower OXTR protein expression with significantly negative correlations between the OXTR protein expression and the CTQ sum score, whereas plasma OXT levels showed no significant differences in association with CM. Lower OXTR protein expression in PBMC were particularly pronounced in the group of insecurely attached mothers compared to the securely attached group. Anxiety levels were significantly higher in CM-affected women. Conclusion: This study demonstrated a significant association between CM and an alteration of OXTR protein expression in human blood cells as a sign for chronic, long-lasting alterations in this attachment-related neurobiological system. PMID:29535656

RPGR-Associated Retinal Degeneration in Human X-Linked RP and a Murine Model

PubMed Central

Huang, Wei Chieh; Wright, Alan F.; Roman, Alejandro J.; Cideciyan, Artur V.; Manson, Forbes D.; Gewaily, Dina Y.; Schwartz, Sharon B.; Sadigh, Sam; Limberis, Maria P.; Bell, Peter; Wilson, James M.; Swaroop, Anand; Jacobson, Samuel G.

2012-01-01

Purpose. We investigated the retinal disease due to mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene in human patients and in an Rpgr conditional knockout (cko) mouse model. Methods. XLRP patients with RPGR-ORF15 mutations (n = 35, ages at first visit 5–72 years) had clinical examinations, and rod and cone perimetry. Rpgr-cko mice, in which the proximal promoter and first exon were deleted ubiquitously, were back-crossed onto a BALB/c background, and studied with optical coherence tomography and electroretinography (ERG). Retinal histopathology was performed on a subset. Results. Different patterns of rod and cone dysfunction were present in patients. Frequently, there were midperipheral losses with residual rod and cone function in central and peripheral retina. Longitudinal data indicated that central rod loss preceded peripheral rod losses. Central cone-only vision with no peripheral function was a late stage. Less commonly, patients had central rod and cone dysfunction, but preserved, albeit abnormal, midperipheral rod and cone vision. Rpgr-cko mice had progressive retinal degeneration detectable in the first months of life. ERGs indicated relatively equal rod and cone disease. At late stages, there was greater inferior versus superior retinal degeneration. Conclusions. RPGR mutations lead to progressive loss of rod and cone vision, but show different patterns of residual photoreceptor disease expression. Knowledge of the patterns should guide treatment strategies. Rpgr-cko mice had onset of degeneration at relatively young ages and progressive photoreceptor disease. The natural history in this model will permit preclinical proof-of-concept studies to be designed and such studies should advance progress toward human therapy. PMID:22807293

Comparative reactivity of human IgE to cynomolgus monkey and human effector cells and effects on IgE effector cell potency

PubMed Central

Saul, Louise; Saul, Louise; Josephs, Debra H; Josephs, Debra H; Cutler, Keith; Cutler, Keith; Bradwell, Andrew; Bradwell, Andrew; Karagiannis, Panagiotis; Karagiannis, Panagiotis; Selkirk, Chris; Selkirk, Chris; Gould, Hannah J; Gould, Hannah J; Jones, Paul; Jones, Paul; Spicer, James F; Spicer, James F; Karagiannis, Sophia N; Karagiannis, Sophia N

2014-01-01

Background: Due to genetic similarities with humans, primates of the macaque genus such as the cynomolgus monkey are often chosen as models for toxicology studies of antibody therapies. IgE therapeutics in development depend upon engagement with the FcεRI and FcεRII receptors on immune effector cells for their function. Only limited knowledge of the primate IgE immune system is available to inform the choice of models for mechanistic and safety evaluations.   Methods: The recognition of human IgE by peripheral blood lymphocytes from cynomolgus monkey and man was compared. We used effector cells from each species in ex vivo affinity, dose-response, antibody-receptor dissociation and potency assays. Results: We report cross-reactivity of human IgE Fc with cynomolgus monkey cells, and comparable binding kinetics to peripheral blood lymphocytes from both species. In competition and dissociation assays, however, human IgE dissociated faster from cynomolgus monkey compared with human effector cells. Differences in association and dissociation kinetics were reflected in effector cell potency assays of IgE-mediated target cell killing, with higher concentrations of human IgE needed to elicit effector response in the cynomolgus monkey system. Additionally, human IgE binding on immune effector cells yielded significantly different cytokine release profiles in each species. Conclusion: These data suggest that human IgE binds with different characteristics to human and cynomolgus monkey IgE effector cells. This is likely to affect the potency of IgE effector functions in these two species, and so has relevance for the selection of biologically-relevant model systems when designing pre-clinical toxicology and functional studies. PMID:24492303

The Role of Peripheral Nerve Function in Age-Related Bone Loss and Changes in Bone Adaptation

DTIC Science & Technology

2014-10-01

and peripheral neuropathy has been identified as an in- dependent predictor of low bone mass in the affected limb of diabetic subjects26. Despite...humans. In: Dyck PJ, Thomas PK, Lambert EH, Bunge P, eds. Peripheral Neuropathy . Philadelphia: WB Saunders; 1984:1103-38. 11. Akopian A, Demulder A...Rix M, Andreassen H, Eskildsen P. Impact of peripheral neuropathy on bone density in patients with type 1 dia- betes. Diabetes Care 1999;22:827-31

Initial analysis of peripheral lymphocytic extracellular signal related kinase activation in autism.

PubMed

Erickson, Craig A; Ray, Balmiki; Wink, Logan K; Bayon, Baindu L; Pedapati, Ernest V; Shaffer, Rebecca; Schaefer, Tori L; Lahiri, Debomoy K

2017-01-01

Dysregulation of extracellular signal-related kinase (ERK) activity has been potentially implicated in the pathophysiology of autistic disorder (autism). ERK is part of a central intracellular signaling cascade responsible for a myriad of cellular functions. ERK is expressed in peripheral blood lymphocytes, and measurement of activated (phosphorylated) lymphocytic ERK is commonly executed in many areas of medicine. We sought to conduct the first study of ERK activation in humans with autism by utilizing a lymphocytic ERK activation assay. We hypothesized that ERK activation would be enhanced in peripheral blood lymphocytes from persons with autism compared to those of neurotypical control subjects. We conducted an initial study of peripheral lymphocyte ERK activation in 45 subjects with autism and 26 age- and gender-matched control subjects (total n = 71). ERK activation was measured using a lymphocyte counting method (primary outcome expressed as lymphocytes staining positive for cytosolic phosphorylated ERK divided by total cells counted) and additional Western blot analysis of whole cell phosphorylated ERK adjusted for total ERK present in the lymphocyte lysate sample. Cytosolic/nuclear localization of pERK activated cells were increased by almost two-fold in the autism subject group compared to matched neurotypical control subjects (cell count ratio of 0.064 ± 0.044 versus 0.034 ± 0.031; p = 0.002). Elevated phosphorylated ERK levels in whole cell lysates also showed increased activated ERK in the autism group compared to controls (n = 54 total) in Western blot analysis. The results of this first in human ERK activation study are consistent with enhanced peripheral lymphocytic ERK activation in autism, as well as suggesting that cellular compartmentalization of activated ERK may be altered in this disorder. Future work will be required to explore the impact of concomitant medication use and other subject characteristics such as level of cognitive functioning on ERK activation. Not applicable. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chronic peripheral inflammation, hippocampal neurogenesis, and behavior.

PubMed

Chesnokova, Vera; Pechnick, Robert N; Wawrowsky, Kolja

2016-11-01

Adult hippocampal neurogenesis is involved in memory and learning, and disrupted neurogenesis is implicated in cognitive impairment and mood disorders, including anxiety and depression. Some long-term peripheral illnesses and metabolic disorders, as well as normal aging, create a state of chronic peripheral inflammation. These conditions are associated with behavioral disturbances linked to disrupted adult hippocampal neurogenesis, such as cognitive impairment, deficits in learning and memory, and depression and anxiety. Pro-inflammatory cytokines released in the periphery are involved in peripheral immune system-to-brain communication by activating resident microglia in the brain. Activated microglia reduce neurogenesis by suppressing neuronal stem cell proliferation, increasing apoptosis of neuronal progenitor cells, and decreasing survival of newly developing neurons and their integration into existing neuronal circuits. In this review, we summarize evolving evidence that the state of chronic peripheral inflammation reduces adult hippocampal neurogenesis, which, in turn, produces the behavioral disturbances observed in chronic inflammatory disorders. As there are no data available on neurogenesis in humans with chronic peripheral inflammatory disease, we focus on animal models and, in parallel, consider the evidence of cognitive disturbance and mood disorders in human patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of 900 MHz Electromagnetic Radiation on the Induction of ROS in Human Peripheral Blood Mononuclear Cells

PubMed Central

Kazemi, E.; Mortazavi, S. M. J.; Ali-Ghanbari, A.; Sharifzadeh, S.; Ranjbaran, R.; Mostafavi-pour, Z.; Zal, F.; Haghani, M.

2015-01-01

Background Despite numerous studies over a decade, it still remains controversial about the biological effects of RF EMF emitted by mobile phone telephony. Objective Here we investigated the effect of 900 MHz GSM on the induction of oxidative stress and the level of intracellular reactive oxygen species (ROS) in human mononuclear cells, monocytes and lymphocytes as defence system cells. Method 6 ml Peripheral Blood samples were obtained from 13 healthy volunteers (21-30 year-old). Each sample was devided into 2 groups: one was exposed RF radiation emitted from a mobile phone simulator for 2 hour and the other used as control group which was not exposed to any fields. After that, mononuclear cells were isolated from peripheral blood by density gradient centrifugation in Ficoll-Paque. The intracellular ROS content in monocytes and lymphocytes was measured by the CM-H2DCFDA fluorescence probe using flowcytometry technique. Results Our results showed significant increase in  ROS production after exposure in population rich in monocytes. This effect was not significant in population rich in lymphocytes in comparison with non exposed cells. Conclusion The results obtained in this study clearly showed the oxidative stress induction capability of RF electromagnetic field in the portion of PBMCs mostly in monocytes, like the case of exposure to micro organisms, although the advantages or disadvantages of this effect should be evaluated. PMID:26396966

Development of Ultra-Super Sensitive Immunohistochemistry and Its Application to the Etiological Study of Adult T-Cell Leukemia/Lymphoma

PubMed Central

Hasui, Kazuhisa; Wang, Jia; Tanaka, Yuetsu; Izumo, Shuji; Eizuru, Yoshito; Matsuyama, Takami

2012-01-01

Antigen retrieval (AR) and ultra-super sensitive immunohistochemistry (ultra-IHC) have been established for application to archival human pathology specimens. The original ultra-IHC was the ImmunoMax method or the catalyzed signal amplification system (ImmunoMax/CSA method), comprising the streptavidin-biotin complex (sABC) method and catalyzed reporter deposition (CARD) reaction with visualization of its deposition. By introducing procedures to diminish non-specific staining in the original ultra-IHC method, we developed the modified ImmunoMax/CSA method with AR heating sections in an AR solution (heating-AR). The heating-AR and modified ImmunoMax/CSA method visualized expression of the predominantly simple present form of HTLV-1 proviral DNA pX region p40Tax protein (Tax) in adult T-cell leukemia/lymphoma (ATLL) cells in archival pathology specimens in approximately 75% of cases. The simple present form of Tax detected exhibited a close relation with ATLL cell proliferation. We also established a new simplified CSA (nsCSA) system by replacing the sABC method with the secondary antibody- and horse radish peroxidase-labeled polymer reagent method, introducing the pretreatments blocking non-specific binding of secondary antibody reagent, and diminishing the diffusion of deposition in the CARD reaction. Combined with AR treating sections with proteinase K solution (enzymatic-AR), the nsCSA system visualized granular immunostaining of the complex present form of Tax in a small number of ATLL cells in most cases, presenting the possibility of etiological pathological diagnosis of ATLL and suggesting that the complex present form of Tax-positive ATLL cells were young cells derived from ATLL stem cells. The heating-AR and ultra-IHC detected physiological expression of the p53 protein and its probable phosphorylation by Tax in peripheral blood mononuclear cells of peripheral blood tissue specimens from HTLV-1 carriers, as well as physiological and pathological expression of the molecules involved with G1 phase progression and G1–S phase transition (E2F-1, E2F-4, DP-1, and cyclin E) in ATLL and peripheral T-cell lymphoma cells. The ultra-IHC with AR is useful for etiological pathological diagnosis of ATLL since HTLV-1 pathogenicity depends on that of Tax, and can be a useful tool for studies translating advanced molecular biology and pathology to human pathology. PMID:22685351

Determination of Zidovudine Triphosphate Intracellular Concentrations in Peripheral Blood Mononuclear Cells from Human Immunodeficiency Virus-Infected Individuals by Tandem Mass Spectrometry

PubMed Central

Font, Eva; Rosario, Osvaldo; Santana, Jorge; García, Hermes; Sommadossi, Jean-Pierre; Rodriguez, Jose F.

1999-01-01

Nucleoside reverse transcriptase inhibitors (NRTIs) used against the human immunodeficiency virus (HIV) need to be activated intracellularly to their triphosphate moiety to inhibit HIV replication. Intracellular concentrations of these NRTI triphosphates, especially zidovudine triphosphate (ZDV-TP), are relatively low (low numbers of femtomoles per 106 cells) in HIV-infected patient peripheral blood mononuclear cells. Recently, several methods have used either high-performance liquid chromatography (HPLC) or solid-phase extraction (SPE) coupled with radioimmunoassay to obtain in vivo measurements of ZDV-TP. The limit of detection (LOD) by these methods ranged from 20 to 200 fmol/106 cells. In this report, we describe the development of a method to determine intracellular ZDV-TP concentrations in HIV-infected patients using SPE and HPLC with tandem mass spectrometry for analysis. The LOD by this method is 4.0 fmol/106 cells with a linear concentration range of at least 4 orders of magnitude from 4.0 to 10,000 fmol/106 cells. In hispanic HIV-infected patients, ZDV-TP was detectable even when the sampling time after drug administration was 15 h. Intracellular ZDV-TP concentrations in these patients ranged from 41 to 193 fmol/106 cells. The low LOD obtained with this method will provide the opportunity for further in vivo pharmacokinetic studies of intracellular ZDV-TP in different HIV-infected populations. Furthermore, this methodology could be used to perform simultaneous detection of two or more NRTIs, such as ZDV-TP and lamivudine triphosphate. PMID:10582890

House Dust Endotoxin and Peripheral Leukocyte Counts: Results from Two Large Epidemiologic Studies

PubMed Central

Carnes, Megan U.; Salo, Päivi M.; Wilkerson, Jesse; Cohn, Richard D.; King, Debra; Hoppin, Jane A.; Sandler, Dale P.; Travlos, Greg; London, Stephanie J.; Thorne, Peter S.; Zeldin, Darryl C.

2017-01-01

Background: The peripheral leukocyte count is a biomarker of inflammation and is associated with human all-cause mortality. Although causes of acute leukocytosis are well-described, chronic environmental determinants of leukocyte number are less well understood. Objectives: We investigated the relationship between house dust endotoxin concentration and peripheral leukocyte counts in human subjects. Methods: The endotoxin–leukocyte relationship was evaluated by linear regression in the National Health and Nutrition Examination Survey (NHANES) 2005–2006 (n=6,254) and the Agricultural Lung Health Study (ALHS; n=1,708). In the ALHS, we tested for a gene [Toll-like Receptor 4 (TLR4), encoding the endotoxin receptor]-by-environment interaction in the endotoxin–leukocyte relationship using regression models with an interaction term. Results: There is a statistically significant, positive association between endotoxin concentration and total leukocyte number [estimated change, 0.186×103/μL (95% CI: 0.070, 0.301×103/μL) per 10-fold change in endotoxin; p=0.004) in the NHANES. Similar positive associations were found for monocytes, lymphocytes, and neutrophils. Stratified analyses revealed possible effect modification by asthma and chronic obstructive pulmonary disease. We observed similar associations in the ALHS. For total leukocytes, there was suggestive evidence in the ALHS of a gene-by-environment interaction for minor allele carrier status at the TLR4 haplotype defined by rs4986790 and rs4986791 (interaction p=0.15). Conclusions: This is, to our knowledge, the first report of an association between house dust endotoxin and leukocyte count in a national survey. The finding was replicated in a farming population. Peripheral leukocyte count may be influenced by residential endotoxin exposure in diverse settings. https://doi.org/10.1289/EHP661 PMID:28599265

Molecular expression in transfected corneal endothelial cells

NASA Astrophysics Data System (ADS)

Wang, Fan; Miao, Zhuang; Lu, Chengwei; Hao, Jilong

2017-10-01

To investigate the capability of human corneal endothelial cells serving as immunological cells. Expression of HLA-DP, -DQ, -DR, CD40, CD80, and CD86 was determined by immunohistochemical methods. Meanwhile, purified peripheral blood mononuclear cells were cocultured with human corneal endothelial cells which were pre-treated with and without -IFN respectively, activation of lymphocytes was determined by FACS analysis. In coculture system, T lymphocyte was activated by corneal endothelial cells, HLA-DP, -DQ, -DR and CD40 expression were increased by - IFN induction. Costimulatory molecular CD80 was shown on the endothelial cells. Human corneal endothelial cells were assumed to be involved in the corneal transplantation rejection process as potential antigen presenting cells.

Acupuncture/Moxibustion RCT for Distal Sensory Peripheral Neuropathy in HIV/AIDS

PubMed Central

Anastasi, Joyce K.; Capili, Bernadette; Chung, Ann M.; Hammerschlag, Richard

2017-01-01

Distal sensory peripheral neuropathy is a common neurological complication experienced by people living with the human immunodeficiency virus (HIV). Traditional Chinese medicine (TCM) may offer effective interventions in the management of its symptoms. To improve the quality and transparency of reporting acupuncture clinical trials, the Consolidated Standards of Reporting Trials (CONSORT) guidelines were developed in 1996 and the Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) recommendations were introduced in 2001. Incorporating international guidelines, this paper describes the development of a RCT including rationale, design, methods, procedures and logistics for a pilot study aimed at evaluating acupuncture and moxibustion for neuropathy associated with HIV. Using STRICTA guidelines as a template, aspects of clinical research design are explored to further optimise future studies of TCM. PMID:29756126

Effect of ultrasonic irradiation on mammalian cells and chromosomes in vitro

NASA Technical Reports Server (NTRS)

Roseboro, J. A.; Buchanan, P.; Norman, A.; Stern, R.

1978-01-01

Human peripheral blood and HeLa cells were irradiated in vitro at the ultrasonic frequency of 65 kHz. The whole blood and HeLa cell suspensions were exposed to continuous and pulsed ultrasonic power levels of 0.12, 0.16, 0.72, 1.12 and 2.24 W for a period of one minute. The method of ultrasonic irradiation was carried out with the whole blood or HeLa cell suspensions coupled directly to a cylindrical transducer while heating of the cell suspensions in excess of 41 C was avoided. Irradiated and unirradiated peripheral blood lymphocyte chromosome cultures were prepared and scored for selected numerical and morphological aberrations. There was no significant difference in the frequency of chromosomal aberrations between irradiated and unirradiated cells.

[Physiological features of skin ageing in human].

PubMed

Tikhonova, I V; Tankanag, A V; Chemeris, N K

2013-01-01

The issue deals with the actual problem of gerontology, notably physiological features of human skin ageing. In the present review the authors have considered the kinds of ageing, central factors, affected on the ageing process (ultraviolet radiation and oxidation stress), as well as the research guidelines of the ageing changes in the skin structure and fuctions: study of mechanical properties, microcirculation, pH and skin thickness. The special attention has been payed to the methods of assessment of skin blood flow, and to results of investigations of age features of peripheral microhemodynamics. The laser Doppler flowmetry technique - one of the modern, noninvasive and extensively used methods for the assessmant of skin blood flow microcirculation system has been expanded in the review. The main results of the study of the ageing changes of skin blood perfusion using this method has been also presented.

Computer-based route-definition system for peripheral bronchoscopy.

PubMed

Graham, Michael W; Gibbs, Jason D; Higgins, William E

2012-04-01

Multi-detector computed tomography (MDCT) scanners produce high-resolution images of the chest. Given a patient's MDCT scan, a physician can use an image-guided intervention system to first plan and later perform bronchoscopy to diagnostic sites situated deep in the lung periphery. An accurate definition of complete routes through the airway tree leading to the diagnostic sites, however, is vital for avoiding navigation errors during image-guided bronchoscopy. We present a system for the robust definition of complete airway routes suitable for image-guided bronchoscopy. The system incorporates both automatic and semiautomatic MDCT analysis methods for this purpose. Using an intuitive graphical user interface, the user invokes automatic analysis on a patient's MDCT scan to produce a series of preliminary routes. Next, the user visually inspects each route and quickly corrects the observed route defects using the built-in semiautomatic methods. Application of the system to a human study for the planning and guidance of peripheral bronchoscopy demonstrates the efficacy of the system.

Genotoxic potential of bee venom (Apis Mellifera) on human peripheral blood lymphocytes in vitro using single cell gel electrophoresis assay.

PubMed

Gajski, Goran; Garaj-Vrhovac, Vera

2008-09-01

Bee venom (BV) has been known to have therapeutic applications in traditional medicine to treat variety of diseases. It is also known that bee venom possesses anti-inflammatory and anticancer effects and that it can inhibit proliferation and induces apoptosis in cancer cells, but there is lack of information regarding genotoxicity of whole bee venom on normal human cells. In the present study, peripheral blood human lymphocytes from healthy donor were exposed in vitro to different concentration (5, 10, 25, 50 and 100 micro g/mL) of whole bee venom at different time periods (1, 6 and 24 hours). The single cell gel electrophoresis (SCGE) assay was used to evaluate the genotoxicity towards human cells. Results showed statistically significant increase in DNA damage caused in BV treated human lymphocytes compared to corresponding control cells for the tail length and tail moment. These results show that the extent of DNA damage, determined by the use of single cell gel electrophoresis is time and dose dependent. Based on the results it is clear that whole bee venom induces DNA damage and has genotoxic potential on human peripheral blood lymphocytes in vitro.

[Establishment and evaluation of an in vitro method for neutrophil extracellular trap generation and degradation].

PubMed

Li, Jinlong; Zhang, Yidan; Zhou, Xin; Ji, Wenjie; Zhao, Jihong; Wei, Luqing; Li, Yuming

2014-09-01

To evaluate a novel method for in vitro generation and degradation of neutrophil extracellular traps (NETs), which are a newly recognized structure that is involved in the pathogenesis of autoimmune diseases and thrombosis. Neutrophils from peripheral blood of healthy donors were obtained by Ficoll-Histopaque gradient separation. NET release was initiated by phorbol myristate acetate (PMA) and validated by immunofluorescence staining and agarose gel electrophoresis. NETs degraded by DNase I and healthy human plasma were quantified by fluorescence spectrometry after staining with PicoGreen. HE staining showed that the purity of neutrophils was up to 95% after Ficoll-Histopaque gradient separation. NET immunofluorescent staining revealed that the network structure was mainly composed of DNA and histones, with molecular length more than 10 kb as demonstrated by agarose gel electrophoresis. Moreover, both DNase and healthy human plasma could induce the degradation of NETs, in varying degrees. This work established an efficient method for in vitro generation and degradation of human NETs.

A Method for Identification and Analysis of Non-Overlapping Myeloid Immunophenotypes in Humans

PubMed Central

Gustafson, Michael P.; Lin, Yi; Maas, Mary L.; Van Keulen, Virginia P.; Johnston, Patrick B.; Peikert, Tobias; Gastineau, Dennis A.; Dietz, Allan B.

2015-01-01

The development of flow cytometric biomarkers in human studies and clinical trials has been slowed by inconsistent sample processing, use of cell surface markers, and reporting of immunophenotypes. Additionally, the function(s) of distinct cell types as biomarkers cannot be accurately defined without the proper identification of homogeneous populations. As such, we developed a method for the identification and analysis of human leukocyte populations by the use of eight 10-color flow cytometric protocols in combination with novel software analyses. This method utilizes un-manipulated biological sample preparation that allows for the direct quantitation of leukocytes and non-overlapping immunophenotypes. We specifically designed myeloid protocols that enable us to define distinct phenotypes that include mature monocytes, granulocytes, circulating dendritic cells, immature myeloid cells, and myeloid derived suppressor cells (MDSCs). We also identified CD123 as an additional distinguishing marker for the phenotypic characterization of immature LIN-CD33+HLA-DR- MDSCs. Our approach permits the comprehensive analysis of all peripheral blood leukocytes and yields data that is highly amenable for standardization across inter-laboratory comparisons for human studies. PMID:25799053

Myokymia and neuromyotonia in veterinary medicine: a comparison with peripheral nerve hyperexcitability syndrome in humans.

PubMed

Vanhaesebrouck, An E; Bhatti, Sofie F M; Franklin, Robin J M; Van Ham, Luc

2013-08-01

Involuntary muscle hyperactivity can result from muscle or peripheral nerve hyperexcitability or central nervous system dysfunction. In humans, diseases causing hyperexcitability of peripheral nerves are grouped together under the term 'peripheral nerve hyperexcitability' (PNH). Hyperexcitability of the peripheral motor nerve can result into five different phenotypic main variants, i.e. fasciculations, myokymia, neuromyotonia, cramps and tetany, each with their own clinical and electromyographic characteristics. This review focuses on the most commonly described expressions of PNH in veterinary medicine, i.e. myokymia and neuromyotonia, in particular in young Jack Russell terriers. Data from 58 veterinary cases with generalized myokymia and neuromyotonia were analyzed, including unpublished treatment and follow-up data on eight Jack Russell terriers from a previous study and seven additional Jack Russell terriers. A dysfunction of the potassium channel or its associated proteins has been found in many human syndromes characterized by PNH, in particular in generalized myokymia and neuromyotonia, and is suspected to occur in veterinary medicine. Potential pathomechanisms of potassium channel dysfunction leading to signs of PNH are broad and include genetic mutations, antibody-mediated attack or ion channel maldistribution due to axonal degeneration or demyelination. A more accurate classification of the different PNH syndromes will facilitate a more rapid diagnosis and guide further research into natural occurring PNH in animals. Copyright © 2013 Elsevier Ltd. All rights reserved.

Valsalva's maneuver revisited: a quantitative method yielding insights into human autonomic control

NASA Technical Reports Server (NTRS)

Smith, M. L.; Beightol, L. A.; Fritsch-Yelle, J. M.; Ellenbogen, K. A.; Porter, T. R.; Eckberg, D. L.

1996-01-01

Seventeen healthy supine subjects performed graded Valsalva maneuvers. In four subjects, transesophageal echographic aortic cross-sectional areas decreased during and increased after straining. During the first seconds of straining, when aortic cross-sectional area was declining and peripheral arterial pressure was rising, peroneal sympathetic muscle neurons were nearly silent. Then, as aortic cross-sectional area and peripheral pressure both declined, sympathetic muscle nerve activity increased, in proportion to the intensity of straining. Poststraining arterial pressure elevations were proportional to preceding increases of sympathetic activity. Sympathetic inhibition after straining persisted much longer than arterial and right atrial pressure elevations. Similarly, R-R intervals changed in parallel with peripheral arterial pressure, until approximately 45 s after the onset of straining, when R-R intervals were greater and arterial pressures were smaller than prestraining levels. Our conclusions are as follows: opposing changes of carotid and aortic baroreceptor inputs reduce sympathetic muscle and increase vagal cardiac motor neuronal firing; parallel changes of barorsensory inputs provoke reciprocal changes of sympathetic and direct changes of vagal firing; and pressure transients lasting only seconds reset arterial pressure-sympathetic and -vagal response relations.

Detection of Sirtuin-1 protein expression in peripheral blood leukocytes in dogs.

PubMed

Yoshimura, Kuniko; Matsuu, Aya; Sasaki, Kai; Momoi, Yasuyuki

2018-05-11

Sirtuin-1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD + )-dependent histone deacetylase with a large number of protein substrates. It has attracted a lot of attention in association with extending lifespan. The objective of this study was to enable the evaluation of SIRT1 expression in peripheral blood mononuclear cells (PBMCs) from dogs by flow cytometry. Three transcript variants were amplified from PBMCs by reverse transcription PCR and the nucleotide sequences were analyzed. On the basis deduced amino acid sequence, a monoclonal antibody against human SIRT1, 1F3, was selected to detect canine SIRT1. Canine SIRT1 in peripheral blood mononuclear cells was successfully detected by western blotting using this antibody. Intracellular canine SIRT1 was also detected in permeabilized 293T cells transfected with a canine SIRT1 expression plasmid by flow cytometry using this antibody. SIRT1 was detected in all leukocyte subsets including lymphocytes, granulocytes and monocytes. The expression level was markedly different among individual dogs. These results indicated that the method applied in this study is useful for evaluating canine SIRT1 levels in PBMCs from dogs.

Use of human peripheral blood lymphocytes to measure DNA binding capacity of chemical carcinogens

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gupta, R.C.; Earley, K.; Sharma, S.

1988-05-01

Although animal models have been used successfully to study metabolic activation and binding of carcinogens to DNA, only limited studies have been done in human systems. To circumvent the problems associated with the inaccessibility of human tissues and a lack of sensitive methods to detect DNA damage, the authors have investigated the capability of human peripheral blood lymphocytes in vitro to metabolize carcinogens to their DNA binding species by a {sup 32}P-labeled adduct assay. Freshly isolated lymphocytes were exposed at 37{degree}C for 18 hr to 4-aminobiphenyl, 2-aminofluorene, 2-anthramine, 2-acetylaminophenanthrene, benzidine, 1-nitropyrene, 1,2-benzanthracene, triphenylene, 7,12-dimethylbenz(a)anthracene, or benzo(a)pyrene at 30 {mu}M each,more » compounds that are shown or suspected to be carcinogenic in experimental animals. The data indicate that all test carcinogens formed readily measurable levels of DNA adducts. Analysis of exposed DNAs by {sup 32}P-labeling after digestion and adduct enrichment showed exclusively or predominantly one major adduct for all test carcinogens, except for 2-anthramine, triphenylene, and 7,12-dimethylbenz(a)anthracene, which showed two or three adducts. From 12 lymphocyte specimens studied thus far, significant interindividual variations were observed. The lymphocyte system in combination with the {sup 32}P-adduct assay may prove to be an ultrasensitive means to determine interindividual variations in the ability to biotransform carcinogens.« less

Both cell fusion and transdifferentiation account for the transformation of human peripheral blood CD34-positive cells into cardiomyocytes in vivo.

PubMed

Zhang, Sui; Wang, Dachun; Estrov, Zeev; Raj, Sean; Willerson, James T; Yeh, Edward T H

2004-12-21

Adult human peripheral blood CD34-positive (CD34+) cells appear to transform into cardiomyocytes in the injured hearts of severe combined immunodeficient mice. It remains unclear, however, whether the apparent transformation is the result of transdifferentiation of the donor stem cells or of fusion of the donor cell with the cardiomyocyte of the recipients. We performed flow cytometry analyses of cells isolated from the hearts of mice that received human CD34+ cells. Human HLA-ABC antigen and cardiac troponin T or Nkx2.5 were used as markers for cardiomyocytes derived from human CD34+ cells, and HLA-ABC and VE-cadherin were used to identify the transformed endothelial cells. The double-positive cells were collected and interphase fluorescence in situ hybridization was used to detect the expression of human and mouse X chromosomes in these cells. We found that 73.3% of nuclei derived from HLA+ and troponin T+ or Nkx2.5+ cardiomyocytes contain both human and mouse X chromosomes and 23.7% contain only human X chromosome. In contrast, the nuclei of HLA-, troponin T+ cells contain only mouse X chromosomes. Furthermore, 97.3% of endothelial cells derived from CD34+ cells contained human X chromosome only. Thus, both cell fusion and transdifferentiation may account for the transformation of peripheral blood CD34+ cells into cardiomyocytes in vivo.

The Use of Blood Vessel–Derived Stem Cells for Meniscal Regeneration and Repair

PubMed Central

OSAWA, AKI; HARNER, CHRISTOPHER D.; GHARAIBEH, BURHAN; MATSUMOTO, TOMOYUKI; MIFUNE, YUTAKA; KOPF, SEBASTIAN; INGHAM, SHEILA J. M.; SCHREIBER, VERENA; USAS, ARVYDAS; HUARD, JOHNNY

2015-01-01

Purpose Surgical repairs of tears in the vascular region of the meniscus usually heal better than repairs performed in the avascular region; thus, we hypothesized that this region might possess a richer supply of vascular-derived stem cells than the avascular region. Methods In this study, we analyzed 6 menisci extracted from aborted human fetuses and 12 human lateral menisci extracted from adult human subjects undergoing total knee arthroplasty. Menisci were immunostained for CD34 (a stem cell marker) and CD146 (a pericyte marker) in situ, whereas other menisci were dissected into two regions (peripheral and inner) and used to isolate meniscus-derived cells by flow cytometry. Cell populations expressing CD34 and CD146 were tested for their multi-lineage differentiation potentials, including chondrogenic, osteogenic, and adipogenic lineages. Fetal peripheral meniscus cells were transplanted by intracapsular injection into the knee joints of an athymic rat meniscal tear model. Rat menisci were extracted and histologically evaluated after 4 wk posttransplantation. Results Immunohistochemistry and flow cytometric analyses demonstrated that a higher number of CD34- and CD146-positive cells were found in the peripheral region compared with the inner region. The CD34- and CD146-positive cells isolated from the vascular region of both fetal and adult menisci demonstrated multilineage differentiation capacities and were more potent than cells isolated from the inner (avascular) region. Fetal CD34- and CD146-positive cells transplanted into the athymic rat knee joint were recruited into the meniscal tear sites and contributed to meniscus repair. Conclusions The vascularized region of the meniscus contains more stem cells than the avascular region. These meniscal-derived stem cells were multi-potent and contributed to meniscal regeneration. PMID:23247715

Role of Semaphorin 7a signaling in TGF-β1 induced lung fibrosis and scleroderma-related interstitial lung disease

PubMed Central

Gan, Ye; Reilkoff, Ronald; Peng, Xueyan; Russell, Thomas; Chen, Qingsheng; Mathai, Susan K.; Homer, Robert; Gulati, Mridu; Siner, Jonathan; Elias, Jack; Bucala, Richard; Herzog, Erica

2012-01-01

Objective Semaphorin (Sema) 7a regulates TGF- β1 induced fibrosis. Using a murine model of pulmonary fibrosis in which an inducible, bioactive form of the human TGF- β1 gene is overexpressed in the lung, we tested the hypothesis that Sema-7a exerts its pro-fibrotic effects in part by promoting the tissue accumulation of CD45+ fibrocytes. Methods Fibrosis and fibrocytes were evaluated in TGF- β1 transgenic mice in which the Sema-7a locus had been disrupted. The effect of replacement or deletion of Sema-7a on bone marrow derived cells was ascertained using bone marrow transplantation. The role of the Sema-7a receptor β1 integrin was assessed using neutralizing antibodies. The applicability of these findings to TGF-β1-driven fibrosis in humans was examined in patients with scleroderma-related interstitial lung disease. Results The appearance of fibrocytes in the lungs in TGF- β1 transgenic mice requires Sema-7a. Replacement of Sema-7a in bone marrow derived cells restores lung fibrosis and fibrocytes. Immunoneutralization of β1 integrin reduces pulmonary fibrocytes and fibrosis. Peripheral blood mononuclear cells from patients with scleroderma-related interstitial lung disease show increased mRNA for Sema-7a and the β1 integrin, with Sema-7a located on collagen producing fibrocytes and CD19+ lymphocytes. Peripheral blood fibrocyte outgrowth is enhanced in these patients. Stimulation of normal human peripheral blood mononuclear cells with recombinant Sema-7a enhances fibrocyte differentiation; these effects are attenuated by β1 integrin neutralization. Conclusion Interventions that reduce Sema-7a expression or prevent the Sema-7a - β1 integrin interaction may be ameliorative in TGF- β1-driven or fibrocyte-associated autoimmune fibroses. PMID:21484765

Hippocampal structure and function are maintained despite severe innate peripheral inflammation.

PubMed

Süß, Patrick; Kalinichenko, Liubov; Baum, Wolfgang; Reichel, Martin; Kornhuber, Johannes; Loskarn, Sandra; Ettle, Benjamin; Distler, Jörg H W; Schett, Georg; Winkler, Jürgen; Müller, Christian P; Schlachetzki, Johannes C M

2015-10-01

Chronic peripheral inflammation mediated by cytokines such as TNFα, IL-1β, and IL-6 is associated with psychiatric disorders like depression and anxiety. However, it remains elusive which distinct type of peripheral inflammation triggers neuroinflammation and affects hippocampal plasticity resulting in depressive-like behavior. We hypothesized that chronic peripheral inflammation in the human TNF-α transgenic (TNFtg) mouse model of rheumatoid arthritis spreads into the central nervous system and induces depressive state manifested in specific behavioral pattern and impaired adult hippocampal neurogenesis. TNFtg mice showed severe erosive arthritis with increased IL-1β and IL-6 expression in tarsal joints with highly elevated human TNF-α levels in the serum. Intriguingly, IL-1β and IL-6 mRNA levels were not altered in the hippocampus of TNFtg mice. In contrast to the pronounced monocytosis in joints and spleen of TNFtg mice, signs of hippocampal microgliosis or astrocytosis were lacking. Furthermore, locomotion was impaired, but there was no locomotion-independent depressive behavior in TNFtg mice. Proliferation and maturation of hippocampal neural precursor cells as well as survival of newly generated neurons were preserved in the dentate gyrus of TNFtg mice despite reduced motor activity and peripheral inflammatory signature. We conclude that peripheral inflammation in TNFtg mice is mediated by chronic activation of the innate immune system. However, severe peripheral inflammation, though impairing locomotor activity, does not elicit depressive-like behavior. These structural and functional findings indicate the maintenance of hippocampal immunity, cellular plasticity, and behavior despite peripheral innate inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

Peripheral Airway Smooth Muscle, but Not the Trachealis, Is Hypercontractile in an Equine Model of Asthma.

PubMed

Matusovsky, Oleg S; Kachmar, Linda; Ijpma, Gijs; Bates, Genevieve; Zitouni, Nedjma; Benedetti, Andrea; Lavoie, Jean-Pierre; Lauzon, Anne-Marie

2016-05-01

Heaves is a naturally occurring equine disease that shares many similarities with human asthma, including reversible antigen-induced bronchoconstriction, airway inflammation, and remodeling. The purpose of this study was to determine whether the trachealis muscle is mechanically representative of the peripheral airway smooth muscle (ASM) in an equine model of asthma. Tracheal and peripheral ASM of heaves-affected horses under exacerbation, or under clinical remission of the disease, and control horses were dissected and freed of epithelium to measure unloaded shortening velocity (Vmax), stress (force/cross-sectional area), methacholine effective concentration at which 50% of the maximum response is obtained, and stiffness. Myofibrillar Mg(2+)-ATPase activity, actomyosin in vitro motility, and contractile protein expression were also measured. Horses with heaves had significantly greater Vmax and Mg(2+)-ATPase activity in peripheral airway but not in tracheal smooth muscle. In addition, a significant correlation was found between Vmax and the time elapsed since the end of the corticosteroid treatment for the peripheral airways in horses with heaves. Maximal stress and stiffness were greater in the peripheral airways of the horses under remission compared with controls and the horses under exacerbation, potentially due to remodeling. Actomyosin in vitro motility was not different between controls and horses with heaves. These data demonstrate that peripheral ASM is mechanically and biochemically altered in heaves, whereas the trachealis behaves as in control horses. It is therefore conceivable that the trachealis muscle may not be representative of the peripheral ASM in human asthma either, but this will require further investigation.

Effects of flaxseed oil on anti-oxidative system and membrane deformation of human peripheral blood erythrocytes in high glucose level

PubMed Central

2012-01-01

Background The erythrocyte membrane lesion is a serious diabetic complication. A number of studies suggested that n-3 fatty acid could reduce lipid peroxidation and elevate α- or γ-tocopherol contents in membrane of erythrocytes. However, evidence regarding the protective effects of flaxseed oil, a natural product rich in n-3 fatty acid, on lipid peroxidation, antioxidative capacity and membrane deformation of erythrocytes exposed to high glucose is limited. Methods Human peripheral blood erythrocytes were isolated and treated with 50 mM glucose to mimic hyperglycemia in the absence or presence of three different doses of flaxseed oil (50, 100 or 200 μM) in the culture medium for 24 h. The malondialdehyde (MDA) and L-glutathione (GSH) were measured by HPLC and LC/MS respectively. The phospholipids symmetry and membrane fatty acid composition of human erythrocytes were detected by flow cytometry and gas chromatograph (GC). The morphology of human erythrocyte was illuminated by ultra scanning electron microscopy. Results Flaxseed oil attenuated hyperglycemia-induced increase of MDA and decrease of GSH in human erythrocytes. Human erythrocytes treated with flaxseed oil contained higher C22:5 and C22:6 than those in the 50 mM glucose control group, indicating that flaxseed oil could reduce lipid asymmetric distribution and membrane perturbation. The ultra scanning electron microscopy and flow cytometer have also indicated that flaxseed oil could protect the membrane of human erythrocytes from deformation at high glucose level. Conclusion The flaxseed oil supplementation may prevent lipid peroxidation and membrane dysfunction of human erythrocytes in hyperglycemia. PMID:22768971

Generation of Induced Pluripotent Stem Cells from Frozen Buffy Coats using Non-integrating Episomal Plasmids.

PubMed

Meraviglia, Viviana; Zanon, Alessandra; Lavdas, Alexandros A; Schwienbacher, Christine; Silipigni, Rosamaria; Di Segni, Marina; Chen, Huei-Sheng Vincent; Pramstaller, Peter P; Hicks, Andrew A; Rossini, Alessandra

2015-06-05

Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by forcing the expression of four transcription factors (Oct-4, Sox-2, Klf-4, and c-Myc), typically expressed by human embryonic stem cells (hESCs). Due to their similarity with hESCs, iPSCs have become an important tool for potential patient-specific regenerative medicine, avoiding ethical issues associated with hESCs. In order to obtain cells suitable for clinical application, transgene-free iPSCs need to be generated to avoid transgene reactivation, altered gene expression and misguided differentiation. Moreover, a highly efficient and inexpensive reprogramming method is necessary to derive sufficient iPSCs for therapeutic purposes. Given this need, an efficient non-integrating episomal plasmid approach is the preferable choice for iPSC derivation. Currently the most common cell type used for reprogramming purposes are fibroblasts, the isolation of which requires tissue biopsy, an invasive surgical procedure for the patient. Therefore, human peripheral blood represents the most accessible and least invasive tissue for iPSC generation. In this study, a cost-effective and viral-free protocol using non-integrating episomal plasmids is reported for the generation of iPSCs from human peripheral blood mononuclear cells (PBMNCs) obtained from frozen buffy coats after whole blood centrifugation and without density gradient separation.

Evaluation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) adduct levels and DNA strand breaks in human peripheral blood lymphocytes exposed in vitro to polycyclic aromatic hydrocarbons with or without animal metabolic activation.

PubMed

Isabel, Rodríguez-Romero María; Sandra, Gómez-Arroyo; Rafael, Villalobos-Pietrini; Carmen, Martínez-Valenzuela; Josefina, Cortés-Eslava; del Carmen, Calderón-Ezquerro María; Rocío, García-Martínez; Francisco, Arenas-Huertero; Elena, Calderón-Segura María

2012-04-01

The polycyclic aromatic hydrocarbons (PAHs) dibenzo(a,h)anthracene, benzo(ghi)perylene, benzo(b)fluoranthene and benzo(a)pyrene have been identified in urban air from Mexico City and some of them are classified as human carcinogens. In the present study, human peripheral blood lymphocytes were exposed in vitro to different concentrations of PAHs with (+S9) or without (-S9) metabolic activation. The genotoxic and cytotoxic effects of each PAH were examined with an alkaline comet assay and trypan blue dye exclusion, and oxidative DNA damage was determined via the detection of 8-hydroxy-2'-deoxyguanosine (8-OhdG) adduct levels by enzyme-linked immunosorbent assay (ELISA). The DNA damage was evaluated with two genotoxicity parameters: the frequency of comets and the comet tail length. Concentrations of 20, 40, 80, 160 and 320 µM DB(a,h)A-S9; 20, 40, 80, 160 and 240 µM B(ghi)P-S9; 20, 30, 40, 60 and 80 µM B(b)F-S9; and 80 µM B(a)P-S9 for 24 h induced a small but significant increase in the means of comet frequency, in the tail length and in the 8-oHDg levels in relation to the control (0.5% DMSO-S9). However, all PAHs+S9 produced a more significant increase in DNA strand breaks and the level of 8-OHdG compared with the control (0.5% DMSO+S9), with a concentration-effect relationship. The viability of lymphocytes exposed to all PAHs-S9 and PAHs+S9 was not modified compared with the control. The results of this study demonstrate that the comet and ELISA are rapid, suitable and sensitive methods to detect in vitro PAH-induced DNA damage in human peripheral lymphocytes.

Presence of human polyomavirus DNA in the peripheral circulation of bone marrow transplant patients with and without hemorrhagic cystitis.

PubMed

Bogdanovic, G; Ljungman, P; Wang, F; Dalianis, T

1996-04-01

In BMT patients, shedding of BK virus (BKV) in the urine has been strongly but not absolutely correlated to hemorrhagic cystitis (HC). The possible presence of human polyomaviruses in peripheral blood leukocytes (PBLs), plasma, serum and urine in BMT patients and an association with HC was investigated by a nested PCR assay. Samples from allogeneic BMT patients with and without HC as well as from autologous BMT patients were analyzed. Human polyomaviruses were detected in urine and blood samples of both allogeneic and autologous BMT patients with and without HC. An association between the presence of a specific human polyomavirus in blood and HC was thus not observed.

Distribution of subpopulations of dendritic cells in peripheral blood of patients treated with exogenous thyrotropin.

PubMed

Stasiołek, Mariusz; Adamczewski, Zbigniew; Puła, Bartosz; Krawczyk-Rusiecka, Kinga; Zygmunt, Arkadiusz; Borowiecka, Magdalena; Dzięgiel, Piotr; Lewiński, Andrzej

2012-11-30

Dendritic cells (DCs) play a major role as regulators of inflammatory events associated with thyroid pathology. The immunoregulatory function of DCs depends strongly on their subtype, as well as maturation and activation status. Numerous hormonal factors modulate the immune properties of DCs, however, little is known about effects exerted by the hypothalamus-pituitary-thyroid-axis. Recently, we have shown a direct regulatory influence of thyroid hormones (TH) on human DCs function. The aim of the present study was to analyze the effect of systemically administered thyrotropin (TSH) on human blood DCs ex vivo. Blood samples for the cytometric analysis of peripheral blood plasmacytoid and myeloid DCs subtypes were collected from patients subjected to total thyroidectomy because of differentiated thyroid carcinoma at 2 time points: (i) directly before the commencement of TSH administration and (ii) 5 days after first TSH injection. The whole blood quantitative and phenotypic analysis of plasmacytoid and myeloid DCs subtypes was performed by flow cytometry. Administration of TSH did not influence the percentage of plasmacytoid DCs in peripheral blood of study participants. Also the percentage of the two main myeloid DCs subpopulations - CD1c/BDCA1+ DCs and CD141/BDCA3+ DCs did not change significantly. TSH administration had no effect on the surface expression of CD86 - one of the major costimulatory molecules - neither in the whole peripheral blood mononuclear cell (PBMC) fraction nor in particular DCs subtypes. In the present study, we demonstrated no influence of systemic TSH administration on human peripheral blood DCs subtypes. These results are in accordance with our previous work suggesting the direct effect of TH on human DCs ex vivo.

Useful method to monitor the physiological effects of alcohol ingestion by combination of micro-integrated laser Doppler blood flow meter and arm-raising test.

PubMed

Iwasaki, Wataru; Nogami, Hirofumi; Ito, Hiroki; Gotanda, Takeshi; Peng, Yao; Takeuchi, Satoshi; Furue, Masutaka; Higurashi, Eiji; Sawada, Renshi

2012-10-01

Alcohol has a variety of effects on the human body, affecting both the sympathetic and parasympathetic nervous system. We examined the peripheral blood flow of alcohol drinkers using a micro-integrated laser Doppler blood flow meter (micro-electromechanical system blood flow sensor). An increased heart rate and blood flow was recorded at the earlobe after alcohol ingestion, and we observed strong correlation between blood flow, heart rate, and breath alcohol content in light drinkers; but not heavy drinkers. We also found that the amplitude of pulse waves measured at the fingertip during an arm-raising test significantly decreased on alcohol consumption, regardless of the individual's alcohol tolerance. Our micro-electromechanical system blood flow sensor successfully detected various physiological changes in peripheral blood circulation induced by alcohol consumption.

Reprogramming of Adult Peripheral Blood Cells into Human Induced Pluripotent Stem Cells as a Safe and Accessible Source of Endothelial Cells.

PubMed

Simara, Pavel; Tesarova, Lenka; Rehakova, Daniela; Farkas, Simon; Salingova, Barbara; Kutalkova, Katerina; Vavreckova, Eva; Matula, Pavel; Matula, Petr; Veverkova, Lenka; Koutna, Irena

2018-01-01

New approaches in regenerative medicine and vasculogenesis have generated a demand for sufficient numbers of human endothelial cells (ECs). ECs and their progenitors reside on the interior surface of blood and lymphatic vessels or circulate in peripheral blood; however, their numbers are limited, and they are difficult to expand after isolation. Recent advances in human induced pluripotent stem cell (hiPSC) research have opened possible avenues to generate unlimited numbers of ECs from easily accessible cell sources, such as the peripheral blood. In this study, we reprogrammed peripheral blood mononuclear cells, human umbilical vein endothelial cells (HUVECs), and human saphenous vein endothelial cells (HSVECs) into hiPSCs and differentiated them into ECs. The phenotype profiles, functionality, and genome stability of all hiPSC-derived ECs were assessed and compared with HUVECs and HSVECs. hiPSC-derived ECs resembled their natural EC counterparts, as shown by the expression of the endothelial surface markers CD31 and CD144 and the results of the functional analysis. Higher expression of endothelial progenitor markers CD34 and kinase insert domain receptor (KDR) was measured in hiPSC-derived ECs. An analysis of phosphorylated histone H2AX (γH2AX) foci revealed that an increased number of DNA double-strand breaks upon reprogramming into pluripotent cells. However, differentiation into ECs restored a normal number of γH2AX foci. Our hiPSCs retained a normal karyotype, with the exception of the HSVEC-derived hiPSC line, which displayed mosaicism due to a gain of chromosome 1. Peripheral blood from adult donors is a suitable source for the unlimited production of patient-specific ECs through the hiPSC interstage. hiPSC-derived ECs are fully functional and comparable to natural ECs. The protocol is eligible for clinical applications in regenerative medicine, if the genomic stability of the pluripotent cell stage is closely monitored.

STUDIES ON THE TREATMENT OF HUMAN TRYPANOSOMIASIS WITH TRYPARSAMIDE (THE SODIUM SALT OF N-PHENYLGLYCINEAMIDE-p-ARSONIC ACID)

PubMed Central

Pearce, Louise

1921-01-01

The present study of the action of tryparsamide in human trypanosomiasis concludes a series of chemical and biological investigations in a particular problem of chemotherapy and thus represents the final step in a logical method of approach to such a problem. It has been shown that tryparsamide, the sodium salt of N-phenylglycineamide-p-arsonic acid, possesses a marked trypanocidal activity in human trypanosomiasis caused by Tr. gambiense. Single doses of from 0.5 to 5.0 gm. produced a peripheral sterilization of lymph glands and blood in an average of 6 to 12 hours. The duration of the peripheral sterilization following single doses of 17 to 83 mg. per kilo ranged from 17 to 58 days in patients who ultimately showed a return of trypanosomes to the peripheral blood. In a number of patients, however, treated with single doses of 9 to 68 mg. per kilo, no such relapse was detected during an observation period of from 40 to 111 days. The drug is extremely soluble in water and may be administered intramuscularly as well as intravenously. The immediate trypanocidal action after intramuscular administration was as rapid as that following the intravenous route while the duration of peripheral sterilization was appreciably longer. Relatively few repeated doses produced in advanced cases a marked and rapid diminution of the cells of the spinal fluid and were associated with definite improvement of mental and nervous symptoms. The occurrence of visual disturbances in certain advanced cases was the only untoward effect detected during the course of the work, and was apparently related to a too frequent administration of the drug. The condition was transitory in the majority of instances and resumption of treatment was not followed by a recurrence of this symptom. The general beneficial effect of the drug was a noticeable feature of its action in both early and advanced cases as shown by the disappearance of subjective symptoms, by the return of the pulse and temperature to normal limits, by the pronounced improvement of the blood picture, and by well marked gains in weight. PMID:19868583

Small-angle neutron scattering study of recombinant yeast-derived human hepatitis B virus surface antigen vaccine particle

NASA Astrophysics Data System (ADS)

Sato, M.; Ito, Y.; Kameyama, K.; Imai, M.; Ishikawa, N.; Takagi, T.

1995-02-01

The overall and internal structure of recombinant yeast-derived human hepatitis B virus surface antigen vaccine particles was investigated by small-angle neutron scattering using the contrast variation method. The vaccine is a nearly spherical particle, and its contrast-matching point was determined to be at about 24% D 2O content, indicating that a large part of the vaccine particle is occupied by lipids and carbohydrates from the yeast. The Stuhrmann plot suggests that the surface antigens exist predominantly in the peripheral region of the particle, which is favorable to the induction of anti-virus antibodies.

Pilot response to peripheral vision cues during instrument flying tasks.

DOT National Transportation Integrated Search

1968-02-01

In an attempt to more closely associate the visual aspects of instrument flying with that of contact flight, a study was made of human response to peripheral vision cues relating to aircraft roll attitude. Pilots, ranging from 52 to 12,000 flying hou...

Molecular analysis of human gamma/delta+ clones from thymus and peripheral blood

PubMed Central

1989-01-01

We analyzed the V gamma and V delta gene usage in TCR-gamma/delta- bearing T cell clones isolated from human peripheral blood and postnatal thymus using V-specific mAbs and Southern and Northern analyses. In peripheral blood most of the gamma/delta cells express the V gamma 9-JP-C gamma 1 chain paired with a delta chain bearing the V delta 2 gene product. This heterodimer is very rare in the postnatal thymus, where a different and less restricted pairing of V gamma 9 and V delta 2 chains is found. These findings indicate that physical constraints cannot explain the overrepresentation of a particular V gamma 9-JP/V delta 2 heterodimer in the peripheral blood, and we discuss alternative mechanisms that may account for this differential distribution. In addition, this analysis allowed us to map the specificity of the delta TCS1 mAb to V delta 1-J delta 1 and to identify at least five different expressed V delta genes. PMID:2572670

New cassane diterpenes from Caesalpinia echinata.

PubMed

Cota, Betania Barros; de Oliveira, Djalma Menezes; de Siqueira, Ezequias Pessoa; Souza-Fagundes, Elaine Maria; Pimenta, Adriano M C; Santos, Daniel M; Rabello, Ana; Zani, Carlos Leomar

2011-10-01

An investigation of the ethanolic extract from stems of Caesalpinia echinata Lam (Leguminosae-Caesalpinioideae) led to the isolation of five new cassane diterpenes along with known lambertianic acid. Their structures were determined based on spectroscopic methods. A preliminary study on leishmanicidal activity demonstrated that compounds 1, 2 and 6 were found to inhibit the growth of amastigote-like forms of Leishmania amazonensis without affecting mononuclear cells obtained from human peripheral blood. Copyright © 2011 Elsevier B.V. All rights reserved.

Neural and hormonal control of food hoarding

PubMed Central

Keen-Rhinehart, E.; Dailey, M. J.; Teubner, B. J.

2011-01-01

Many animals hoard food, including humans, but despite its pervasiveness, little is known about the physiological mechanisms underlying this appetitive behavior. We summarize studies of food hoarding in humans and rodents with an emphasis on mechanistic laboratory studies of species where this behavior importantly impacts their energy balance (hamsters), but include laboratory rat studies although their wild counterparts do not hoard food. The photoperiod and cold can affect food hoarding, but food availability is the most significant environmental factor affecting food hoarding. Food-deprived/restricted hamsters and humans exhibit large increases in food hoarding compared with their fed counterparts, both doing so without overeating. Some of the peripheral and central peptides involved in food intake also affect food hoarding, although many have not been tested. Ad libitum-fed hamsters given systemic injections of ghrelin, the peripheral orexigenic hormone that increases with fasting, mimics food deprivation-induced increases in food hoarding. Neuropeptide Y or agouti-related protein, brain peptides stimulated by ghrelin, given centrally to ad libitum-fed hamsters, duplicates the early and prolonged postfood deprivation increases in food hoarding, whereas central melanocortin receptor agonism tends to inhibit food deprivation and ghrelin stimulation of hoarding. Central or peripheral leptin injection or peripheral cholecystokinin-33, known satiety peptides, inhibit food hoarding. Food hoarding markedly increases with pregnancy and lactation. Because fasted and/or obese humans hoard more food in general, and more high-density/high-fat foods specifically, than nonfasted and/or nonobese humans, understanding the mechanisms underlying food hoarding could provide another target for behavioral/pharmacological approaches to curb obesity. PMID:21653877

Impact of peripheral hearing loss on top-down auditory processing.

PubMed

Lesicko, Alexandria M H; Llano, Daniel A

2017-01-01

The auditory system consists of an intricate set of connections interposed between hierarchically arranged nuclei. The ascending pathways carrying sound information from the cochlea to the auditory cortex are, predictably, altered in instances of hearing loss resulting from blockage or damage to peripheral auditory structures. However, hearing loss-induced changes in descending connections that emanate from higher auditory centers and project back toward the periphery are still poorly understood. These pathways, which are the hypothesized substrate of high-level contextual and plasticity cues, are intimately linked to the ascending stream, and are thereby also likely to be influenced by auditory deprivation. In the current report, we review both the human and animal literature regarding changes in top-down modulation after peripheral hearing loss. Both aged humans and cochlear implant users are able to harness the power of top-down cues to disambiguate corrupted sounds and, in the case of aged listeners, may rely more heavily on these cues than non-aged listeners. The animal literature also reveals a plethora of structural and functional changes occurring in multiple descending projection systems after peripheral deafferentation. These data suggest that peripheral deafferentation induces a rebalancing of bottom-up and top-down controls, and that it will be necessary to understand the mechanisms underlying this rebalancing to develop better rehabilitation strategies for individuals with peripheral hearing loss. Copyright © 2016 Elsevier B.V. All rights reserved.

Direct Conversion of Human Fibroblasts into Schwann Cells that Facilitate Regeneration of Injured Peripheral Nerve In Vivo

PubMed Central

Sowa, Yoshihiro; Kishida, Tsunao; Tomita, Koichi; Yamamoto, Kenta; Numajiri, Toshiaki

2017-01-01

Abstract Schwann cells (SCs) play pivotal roles in the maintenance and regeneration of the peripheral nervous system. Although transplantation of SCs enhances repair of experimentally damaged peripheral and central nerve tissues, it is difficult to prepare a sufficient number of functional SCs for transplantation therapy without causing adverse events for the donor. Here, we generated functional SCs by somatic cell reprogramming procedures and demonstrated their capability to promote peripheral nerve regeneration. Normal human fibroblasts were phenotypically converted into SCs by transducing SOX10 and Krox20 genes followed by culturing for 10 days resulting in approximately 43% directly converted Schwann cells (dSCs). The dSCs expressed SC‐specific proteins, secreted neurotrophic factors, and induced neuronal cells to extend neurites. The dSCs also displayed myelin‐forming capability both in vitro and in vivo. Moreover, transplantation of the dSCs into the transected sciatic nerve in mice resulted in significantly accelerated regeneration of the nerve and in improved motor function at a level comparable to that with transplantation of the SCs obtained from a peripheral nerve. The dSCs induced by our procedure may be applicable for novel regeneration therapy for not only peripheral nerve injury but also for central nerve damage and for neurodegenerative disorders related to SC dysfunction. Stem Cells Translational Medicine 2017;6:1207–1216 PMID:28186702

21 CFR 876.5310 - Nonimplanted, peripheral electrical continence device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nonimplanted, peripheral electrical continence device. 876.5310 Section 876.5310 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876...

21 CFR 1271.420 - HCT/Ps offered for import.

Code of Federal Regulations, 2010 CFR

2010-04-01

... recipient for reproductive use. (d) This section does not apply to peripheral blood stem/progenitor cells... peripheral blood stem/progenitor cells may present an unreasonable risk of communicable disease transmission...) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN CELLS, TISSUES...

21 CFR 1271.420 - HCT/Ps offered for import.

Code of Federal Regulations, 2011 CFR

2011-04-01

... recipient for reproductive use. (d) This section does not apply to peripheral blood stem/progenitor cells... peripheral blood stem/progenitor cells may present an unreasonable risk of communicable disease transmission...) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN CELLS, TISSUES...

21 CFR 1271.420 - HCT/Ps offered for import.

Code of Federal Regulations, 2014 CFR

2014-04-01

... recipient for reproductive use. (d) This section does not apply to peripheral blood stem/progenitor cells... peripheral blood stem/progenitor cells may present an unreasonable risk of communicable disease transmission...) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN CELLS, TISSUES...

21 CFR 1271.420 - HCT/Ps offered for import.

Code of Federal Regulations, 2013 CFR

2013-04-01

... recipient for reproductive use. (d) This section does not apply to peripheral blood stem/progenitor cells... peripheral blood stem/progenitor cells may present an unreasonable risk of communicable disease transmission...) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN CELLS, TISSUES...

21 CFR 1271.420 - HCT/Ps offered for import.

Code of Federal Regulations, 2012 CFR

2012-04-01

... recipient for reproductive use. (d) This section does not apply to peripheral blood stem/progenitor cells... peripheral blood stem/progenitor cells may present an unreasonable risk of communicable disease transmission...) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN CELLS, TISSUES...

21 CFR 876.5310 - Nonimplanted, peripheral electrical continence device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Nonimplanted, peripheral electrical continence device. 876.5310 Section 876.5310 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876...

Inhibition of Acute in vivo Human Immunodeficiency Virus Infection by Human Interleukin 10 Treatment of SCID Mice Implanted with Human Fetal Thymus and Liver

NASA Astrophysics Data System (ADS)

Kollmann, Tobias R.; Pettoello-Mantovani, Massimo; Katopodis, Nikos F.; Hachamovitch, Moshe; Rubinstein, Arye; Kim, Ana; Goldstein, Harris

1996-04-01

To improve the usefulness of in vivo models for the investigation of the pathophysiology of human immunodeficiency virus (HIV) infection, we modified the construction of SCID mice implanted with human fetal thymus and liver (thy/liv-SCID-hu mice) so that the peripheral blood of the mice contained significant numbers of human monocytes and T cells. After inoculation with HIV-159, a primary patient isolate capable of infecting monocytes and T cells, the modified thy/liv-SCID-hu mice developed disseminated HIV infection that was associated with plasma viremia. The development of plasma viremia and HIV infection in thy/liv-SCID-hu mice inoculated with HIV-159 was inhibited by acute treatment with human interleukin (IL) 10 but not with human IL-12. The human peripheral blood mononuclear cells in these modified thy/liv-SCID-hu mice were responsive in vivo to treatment with exogenous cytokines. Human interferon γ expression in the circulating human peripheral blood mononuclear cells was induced by treatment with IL-12 and inhibited by treatment with IL-10. Thus, these modified thy/liv-SCID-hu mice should prove to be a valuable in vivo model for examining the role of immunomodulatory therapy in modifying HIV infection. Furthermore, our demonstration of the in vivo inhibitory effect of IL-10 on acute HIV infection suggests that further studies may be warranted to evaluate whether there is a role for IL-10 therapy in preventing HIV infection in individuals soon after exposure to HIV such as for children born to HIV-infected mothers.

Bioavailability of insulin detemir and human insulin at the level of peripheral interstitial fluid in humans, assessed by open-flow microperfusion.

PubMed

Bodenlenz, M; Ellmerer, M; Schaupp, L; Jacobsen, L V; Plank, J; Brunner, G A; Wutte, A; Aigner, B; Mautner, S I; Pieber, T R

2015-12-01

To find an explanation for the lower potency of insulin detemir observed in humans compared with unmodified human insulin by investigating insulin detemir and human insulin concentrations directly at the level of peripheral insulin-sensitive tissues in humans in vivo. Euglycaemic-hyperinsulinaemic clamp experiments were performed in healthy volunteers. Human insulin was administered i.v. at 6 pmol/kg/min and insulin detemir at 60 pmol/kg/min, achieving a comparable steady-state pharmacodynamic action. In addition, insulin detemir was doubled to 120 pmol/kg/min. Minimally invasive open-flow microperfusion (OFM) sampling methodology was combined with inulin calibration to quantify human insulin and insulin detemir in the interstitial fluid (ISF) of subcutaneous adipose and skeletal muscle tissue. The human insulin concentration in the ISF was ∼115 pmol/l or ∼30% of the serum concentration, whereas the insulin detemir concentration in the ISF was ∼680 pmol/l or ∼2% of the serum concentration. The molar insulin detemir interstitial concentration was five to six times higher than the human insulin interstitial concentration and metabolic clearance of insulin detemir from serum was substantially reduced compared with human insulin. OFM proved useful for target tissue measurements of human insulin and the analogue insulin detemir. Our tissue data confirm a highly effective retention of insulin detemir in the vascular compartment. The higher insulin detemir relative to human insulin tissue concentrations at comparable pharmacodynamics, however, indicate that the lower potency of insulin detemir in humans is attributable to a reduced effect in peripheral insulin-sensitive tissues and is consistent with the reduced in vitro receptor affinity. © 2015 John Wiley & Sons Ltd.

Comparing the Hematopoetic Syndrome Time Course in the NHP Animal Model to Radiation Accident Cases From the Database Search.

PubMed

Graessle, Dieter H; Dörr, Harald; Bennett, Alexander; Shapiro, Alla; Farese, Ann M; MacVittie, Thomas J; Meineke, Viktor

2015-11-01

Since controlled clinical studies on drug administration for the acute radiation syndrome are lacking, clinical data of human radiation accident victims as well as experimental animal models are the main sources of information. This leads to the question of how to compare and link clinical observations collected after human radiation accidents with experimental observations in non-human primate (NHP) models. Using the example of granulocyte counts in the peripheral blood following radiation exposure, approaches for adaptation between NHP and patient databases on data comparison and transformation are introduced. As a substitute for studying the effects of administration of granulocyte-colony stimulating factor (G-CSF) in human clinical trials, the method of mathematical modeling is suggested using the example of G-CSF administration to NHP after total body irradiation.

Molecular cloning of human T-cell lymphotrophic virus type I-like proviral genome from the peripheral lymphocyte DNA of a patient with chronic neurologic disorders.

PubMed Central

Reddy, E P; Mettus, R V; DeFreitas, E; Wroblewska, Z; Cisco, M; Koprowski, H

1988-01-01

Human T-cell lymphotropic virus type 1 (HTLV-I), the etiologic agent of human T-cell leukemia, has recently been shown to be associated with neurologic disorders such as tropical spastic paraparesis, HTLV-associated myelopathy, and possibly with multiple sclerosis. In this communication, we have examined one specific case of neurologic disorder that can be classified as multiple sclerosis or tropical spastic paraparesis. The patient suffering from chronic neurologic disorder was found to contain antibodies to HTLV-I envelope and gag proteins in his serum and cerebrospinal fluid. Lymphocytes from peripheral blood and cerebrospinal fluid of the patient were shown to express viral RNA sequences by in situ hybridization. Southern blot analysis of the patient lymphocyte DNA revealed the presence of HTLV-I-related sequences. Blot-hybridization analysis of the RNA from fresh peripheral lymphocytes stimulated with interleukin 2 revealed the presence of abundant amounts of genomic viral RNA with little or no subgenomic RNA. We have cloned the proviral genome from the DNA of the peripheral lymphocytes and determined its restriction map. This analysis shows that this proviral genome is very similar if not identical to that of the prototype HTLV-I genome. Images PMID:2897123

[Peripheral neuropathy and blood-nerve barrier].

PubMed

Kanda, Takashi

2009-11-01

It is important to know the cellular properties of endoneurial microvascular endothelial cells (PnMECs) and microvascular pericytes which constitute blood-nerve barrier (BNB), since this barrier structure in the peripheral nervous system (PNS) may play pivotal pathophysiological roles in various disorders of the PNS including inflammatory neuropathies (i.e. Guillain-Barré syndrome), vasculitic neuropathies, hereditary neuropathies and diabetic neuropathy. However, in contrast to blood-brain barrier (BBB), very few studies have been directed to BNB and no adequate cell lines originating from BNB had been launched. In our laboratory, we successfully established human immortalized cell lines originating from BNB using temperature-sensitive SV40 large T antigen and the cellular properties of human cell lines are presented in this paper. Human PnMEC cell line showed high transendothelial electrical resistance and expressed tight junction components and various types of influx as well as efflux transporters that have been reported to function at BBB. Human pericyte cell line also possessed tight junction proteins except claudin-5 and secrete various cytokines and growth factors including bFGF, VEGF, GDNF, NGF, BDNF and angiopoietin-1. Co-culture with pericytes or pericyte-conditioned media strengthend barrier properties of PnMEC, suggesting that in the PNS, peripheral nerve pericytes support the BNB function and play the same role of astrocytes in the BBB. Future accumulation of the knowledge concerning the cellular properties of BNB-forming cells will open the door to novel therapeutic strategies for intractable peripheral neuropathies.

The Human Cutaneous Chemokine System

PubMed Central

McCully, Michelle L.; Moser, Bernhard

2011-01-01

Irrespective of the immune status, the vast majority of all lymphocytes reside in peripheral tissues whereas those present in blood only amount to a small fraction of the total. It has been estimated that T cells in healthy human skin outnumber those present in blood by at least a factor of two. How lymphocytes within these two compartments relate to each other is not well understood. However, mounting evidence suggest that the study of T cell subsets present in peripheral blood does not reflect the function of their counterparts at peripheral sites. This is especially true under steady-state conditions whereby long-lived memory T cells in healthy tissues, notably those in epithelial tissues at body surfaces, are thought to fulfill a critical immune surveillance function by contributing to the first line of defense against a series of local threats, including microbes, tumors, and toxins, and by participating in wound healing. The relative scarcity of information regarding peripheral T cells and the factors regulating their localization is primarily due to inherent difficulties in obtaining healthy tissue for the extraction and study of immune cells on a routine basis. This is most certainly true for humans. Here, we review our current understanding of T cell homing to human skin and compare it when possible with gut-selective homing. We also discuss candidate chemokines that may account for the tissue selectivity in this process and present a model whereby CCR8, and its ligand CCL1, selectively regulate the homeostatic migration of memory lymphocytes to skin tissue. PMID:22566823

EZ spheres: a stable and expandable culture system for the generation of pre-rosette multipotent stem cells from human ESCs and iPSCs.

PubMed

Ebert, Allison D; Shelley, Brandon C; Hurley, Amanda M; Onorati, Marco; Castiglioni, Valentina; Patitucci, Teresa N; Svendsen, Soshana P; Mattis, Virginia B; McGivern, Jered V; Schwab, Andrew J; Sareen, Dhruv; Kim, Ho Won; Cattaneo, Elena; Svendsen, Clive N

2013-05-01

We have developed a simple method to generate and expand multipotent, self-renewing pre-rosette neural stem cells from both human embryonic stem cells (hESCs) and human induced pluripotent stem cells (iPSCs) without utilizing embryoid body formation, manual selection techniques, or complex combinations of small molecules. Human ESC and iPSC colonies were lifted and placed in a neural stem cell medium containing high concentrations of EGF and FGF-2. Cell aggregates (termed EZ spheres) could be expanded for long periods using a chopping method that maintained cell-cell contact. Early passage EZ spheres rapidly down-regulated OCT4 and up-regulated SOX2 and nestin expression. They retained the potential to form neural rosettes and consistently differentiated into a range of central and peripheral neural lineages. Thus, they represent a very early neural stem cell with greater differentiation flexibility than other previously described methods. As such, they will be useful for the rapidly expanding field of neurological development and disease modeling, high-content screening, and regenerative therapies based on pluripotent stem cell technology. Copyright © 2013 Elsevier B.V. All rights reserved.

Retinal ganglion cell dendritic fields in old-world monkeys are oriented radially.

PubMed

Schall, J D; Perry, V H; Leventhal, A G

1986-03-12

We analyzed the dendritic field morphology of 297 ganglion cells from peripheral regions of monkey retina. Most of the dendritic fields were elongated, and there was a significant tendency for the dendritic fields to be oriented radially, i.e., like the spokes of a wheel with the fovea at the hub. An overrepresentation of radial orientations in the peripheral retina of primates might explain why humans are best able to detect stimuli which are oriented radially using peripheral vision.

Are visual peripheries forever young?

PubMed

Burnat, Kalina

2015-01-01

The paper presents a concept of lifelong plasticity of peripheral vision. Central vision processing is accepted as critical and irreplaceable for normal perception in humans. While peripheral processing chiefly carries information about motion stimuli features and redirects foveal attention to new objects, it can also take over functions typical for central vision. Here I review the data showing the plasticity of peripheral vision found in functional, developmental, and comparative studies. Even though it is well established that afferent projections from central and peripheral retinal regions are not established simultaneously during early postnatal life, central vision is commonly used as a general model of development of the visual system. Based on clinical studies and visually deprived animal models, I describe how central and peripheral visual field representations separately rely on early visual experience. Peripheral visual processing (motion) is more affected by binocular visual deprivation than central visual processing (spatial resolution). In addition, our own experimental findings show the possible recruitment of coarse peripheral vision for fine spatial analysis. Accordingly, I hypothesize that the balance between central and peripheral visual processing, established in the course of development, is susceptible to plastic adaptations during the entire life span, with peripheral vision capable of taking over central processing.

Synthesis of antimicrobial silver nanoparticles through a photomediated reaction in an aqueous environment.

PubMed

Banasiuk, Rafał; Frackowiak, Joanna E; Krychowiak, Marta; Matuszewska, Marta; Kawiak, Anna; Ziabka, Magdalena; Lendzion-Bielun, Zofia; Narajczyk, Magdalena; Krolicka, Aleksandra

2016-01-01

A fast, economical, and reproducible method for nanoparticle synthesis has been developed in our laboratory. The reaction is performed in an aqueous environment and utilizes light emitted by commercially available 1 W light-emitting diodes (λ =420 nm) as the catalyst. This method does not require nanoparticle seeds or toxic chemicals. The irradiation process is carried out for a period of up to 10 minutes, significantly reducing the time required for synthesis as well as environmental impact. By modulating various reaction parameters silver nanoparticles were obtained, which were predominantly either spherical or cubic. The produced nanoparticles demonstrated strong antimicrobial activity toward the examined bacterial strains. Additionally, testing the effect of silver nanoparticles on the human keratinocyte cell line and human peripheral blood mononuclear cells revealed that their cytotoxicity may be limited by modulating the employed concentrations of nanoparticles.

Failure to Detect Borna Disease Virus Antibody and RNA from Peripheral Blood Mononuclear Cells of Psychiatric Patients

PubMed Central

Na, Kyoung-Sae; Tae, Seong-Ho; Song, Jin-won

2009-01-01

Objective Borna disease virus (BDV) is a highly neurotropic agent causing various neuropsychiatric symptoms in animals. Over the past two decades, it has been suggested that BDV might be associated with human psychiatric diseases. We aimed to investigate whether BDV is associated with psychiatric patients in Korea. Methods We recruited 60 normal controls and 198 psychiatric patients (98 patients with depressive disorder, 60 with schizophrenia, and 40 with bipolar disorder). We used an indirect immunofluorescence antibody (IFA) test for the BDV antibody and a real-time reverse transcriptase polymerase chain reaction (rRT-PCR) assay for p24 and p40 RNA from peripheral blood mononuclear cells (PBMCs). Results Neither the BDV antibody nor p24, p40 RNA was detected in controls and patients groups. Conclusion Our results suggest that BDV might not be associated with psychiatric patients in Korea. PMID:20140130

In Vivo Hypermutation of Xenotropic Murine Leukemia Virus-Related Virus DNA in Peripheral Blood Mononuclear Cells of Rhesus Macaque by APOBEC3 Proteins

PubMed Central

Zhang, Ao; Bogerd, Hal; Villinger, Francois; Gupta, Jaydip Das; Dong, Beihua; Klein, Eric A.; Hackett, John; Schochetman, Gerald; Cullen, Bryan R.; Silverman, Robert H.

2011-01-01

The gammaretrovirus, xenotropic murine leukemia virus-related virus (XMRV), replicates to high titers in some human cell lines and is able to infect non-human primates. To determine whether APOBEC3 (A3) proteins restrict XMRV infections in a non-human primate model, we sequenced proviral DNA from peripheral blood mononuclear cells of XMRV-infected rhesus macaques. Hypermutation characteristic of A3DE, A3F and A3G activities was observed in the XMRV proviral sequences in vivo. Furthermore, expression of rhesus A3DE, A3F, or A3G in human cells inhibited XMRV infection and caused hypermutation of XMRV DNA. These studies show that some rhesus A3 isoforms are highly effective against XMRV in the blood of a non-human primate model of infection and in cultured human cells. PMID:21982221

Ozone Exposure Increases Circulating Stress Hormones and Lipid Metabolites in Humans

PubMed Central

Miller, Desinia B.; Ghio, Andrew J.; Karoly, Edward D.; Bell, Lauren N.; Snow, Samantha J.; Madden, Michael C.; Soukup, Joleen; Cascio, Wayne E.; Gilmour, M. Ian

2016-01-01

Rationale: Air pollution has been associated with increased prevalence of type 2 diabetes; however, the mechanisms remain unknown. We have shown that acute ozone exposure in rats induces release of stress hormones, hyperglycemia, leptinemia, and glucose intolerance that are associated with global changes in peripheral glucose, lipid, and amino acid metabolism. Objectives: To examine ozone-induced metabolic derangement in humans using serum metabolomic assessment, establish human-to-rodent coherence, and identify novel nonprotein biomarkers. Methods: Serum samples were obtained from a crossover clinical study that included two clinic visits (n = 24 each) where each subject was blindly exposed in the morning to either filtered air or 0.3 parts per million ozone for 2 hours during 15-minute on-off exercise. Serum samples collected within 1 hour after exposure were assessed for changes in metabolites using a metabolomic approach. Measurements and Main Results: Metabolomic analysis revealed that ozone exposure markedly increased serum cortisol and corticosterone together with increases in monoacylglycerol, glycerol, and medium- and long-chain free fatty acids, reflective of lipid mobilization and catabolism. Additionally, ozone exposure increased serum lysolipids, potentially originating from membrane lipid breakdown. Ozone exposure also increased circulating mitochondrial β-oxidation–derived metabolites, such as acylcarnitines, together with increases in the ketone body 3-hydroxybutyrate. These changes suggested saturation of β-oxidation by ozone in exercising humans. Conclusions: As in rodents, acute ozone exposure increased stress hormones and globally altered peripheral lipid metabolism in humans, likely through activation of a neurohormonally mediated stress response pathway. The metabolomic assessment revealed new biomarkers and allowed for establishment of rodent-to-human coherence. Clinical trial registered with www.clinicaltrials.gov (NCT 01492517). PMID:26745856

Exploring pain pathophysiology in patients.

PubMed

Sommer, Claudia

2016-11-04

Although animal models of pain have brought invaluable information on basic processes underlying pain pathophysiology, translation to humans is a problem. This Review will summarize what information has been gained by the direct study of patients with chronic pain. The techniques discussed range from patient phenotyping using quantitative sensory testing to specialized nociceptor neurophysiology, imaging methods of peripheral nociceptors, analyses of body fluids, genetics and epigenetics, and the generation of sensory neurons from patients via inducible pluripotent stem cells. Copyright © 2016, American Association for the Advancement of Science.

Raman spectroscopic detection of peripheral nerves towards nerve-sparing surgery

NASA Astrophysics Data System (ADS)

Minamikawa, Takeo; Harada, Yoshinori; Takamatsu, Tetsuro

2017-02-01

The peripheral nervous system plays an important role in motility, sensory, and autonomic functions of the human body. Preservation of peripheral nerves in surgery, namely nerve-sparing surgery, is now promising technique to avoid functional deficits of the limbs and organs following surgery as an aspect of the improvement of quality of life of patients. Detection of peripheral nerves including myelinated and unmyelinated nerves is required for the nerve-sparing surgery; however, conventional nerve identification scheme is sometimes difficult to identify peripheral nerves due to similarity of shape and color to non-nerve tissues or its limited application to only motor peripheral nerves. To overcome these issues, we proposed a label-free detection technique of peripheral nerves by means of Raman spectroscopy. We found several fingerprints of peripheral myelinated and unmyelinated nerves by employing a modified principal component analysis of typical spectra including myelinated nerve, unmyelinated nerve, and adjacent tissues. We finally realized the sensitivity of 94.2% and the selectivity of 92.0% for peripheral nerves including myelinated and unmyelinated nerves against adjacent tissues. Although further development of an intraoperative Raman spectroscopy system is required for clinical use, our proposed approach will serve as a unique and powerful tool for peripheral nerve detection for nerve-sparing surgery in the future.

Olive Oil Phenolics Prevent Oxysterol‐Induced Proinflammatory Cytokine Secretion and Reactive Oxygen Species Production in Human Peripheral Blood Mononuclear Cells, Through Modulation of p38 and JNK Pathways

PubMed Central

Deiana, Monica; Spencer, Jeremy P. E.; Corona, Giulia

2017-01-01

Scope The aim of the present study was to investigate the ability of extra virgin olive oil (EVOO) polyphenols to counteract the proinflammatory effects induced by dietary and endogenous oxysterols in ex vivo immune cells. Methods and results Peripheral blood mononuclear cells (PBMCs), separated from the whole blood of healthy donors, were utilized and were stimulated with an oxysterols mixture, in the presence of physiologically relevant concentrations of the EVOO polyphenols, hydroxytyrosol, tyrosol, and homovanillic alcohol. Oxysterols significantly increased the production of proinflammatory cytokines, interleukin‐1β, regulated on activation, normal T‐cell expressed and secreted and macrophage migration inhibitory factor in ex vivo cultured PBMCs. Increased levels of reactive oxygen species (ROS) were also detected along with increased phosphorylation of the p38 and JNK. All phenolic compounds significantly reduced cytokine secretion induced by the oxysterols and inhibited ROS production and mitogen activated protein kinase phosphorylation. Conclusions These results suggest that extra virgin olive oil polyphenols modulate the immune response induced by dietary and endogenous cholesterol oxidation products in human immune cells and may hold benefit in controlling chronic immune and/or inflammatory processes. PMID:28815947

Periodontal disease associates with higher brain amyloid load in normal elderly

PubMed Central

Kamer, Angela R.; Pirraglia, Elizabeth; Tsui, Wai; Rusinek, Henry; Vallabhajosula, Shankar; Mosconi, Lisa; Yi, Li; McHugh, Pauline; Craig, Ronald G.; Svetcov, Spencer; Linker, Ross; Shi, Chen; Glodzik, Lidia; Williams, Schantel; Corby, Patricia; Saxena, Deepak; de Leon, Mony J.

2015-01-01

Background The accumulation of amyloid β plaques (Aβ) is a central feature of Alzheimer’s disease (AD). First reported in animal models, it remains uncertain if peripheral inflammatory/infectious conditions in humans can promote Aβ brain accumulation. Periodontal disease, a common chronic infection, has been previously reported to be associated with AD. Methods Thirty-eight cognitively normal, healthy, community residing elderly (mean age 61; 68% female) were examined in an Alzheimer’s Disease research center and a University-based Dental School. Linear regression models (adjusted for age, ApoE and smoking) were used to test the hypothesis that periodontal disease assessed by clinical attachment loss was associated with brain Aβ load using 11C-PIB PET imaging. Results After adjusting for confounders, clinical attachment loss (≥ 3mm), representing a history of periodontal inflammatory/infectious burden, was associated with increased 11C-PIB uptake in Aβ vulnerable brain regions (p=0.002). Conclusion We show for the first time in humans an association between periodontal disease and brain Aβ load. These data are consistent with prior animal studies showing that peripheral inflammation/infections are sufficient to produce brain Aβ accumulations. PMID:25491073

Ixodes scapularis saliva mitigates inflammatory cytokine secretion during Anaplasma phagocytophilum stimulation of immune cells

PubMed Central

2012-01-01

Background Ixodes scapularis saliva enables the transmission of infectious agents to the mammalian host due to its immunomodulatory, anesthetic and anti-coagulant properties. However, how I. scapularis saliva influences host cytokine secretion in the presence of the obligate intracellular rickettsial pathogen Anaplasma phagocytophilum remains elusive. Methods Bone marrow derived macrophages (BMDMs) were stimulated with pathogen associated molecular patterns (PAMPs) and A. phagocytophilum. Cytokine secretion was measured in the presence and absence of I. scapularis saliva. Human peripheral blood mononuclear cells (PBMCs) were also stimulated with Tumor Necrosis Factor (TNF)-α in the presence and absence of I. scapularis saliva and interleukin (IL)-8 was measured. Results I. scapularis saliva inhibits inflammatory cytokine secretion by macrophages during stimulation of Toll-like (TLR) and Nod-like receptor (NLR) signaling pathways. The effect of I. scapularis saliva on immune cells is not restricted to murine macrophages because decreasing levels of interleukin (IL)-8 were observed after TNF-α stimulation of human peripheral blood mononuclear cells. I. scapularis saliva also mitigates pro-inflammatory cytokine response by murine macrophages during challenge with A. phagocytophilum. Conclusions These findings suggest that I. scapularis may inhibit inflammatory cytokine secretion during rickettsial transmission at the vector-host interface. PMID:23050849

Separation of human CD4+CD39+ T cells by magnetic beads reveals two phenotypically and functionally different subsets

PubMed Central

Schuler, Patrick J.; Harasymczuk, Malgorzata; Schilling, Bastian; Lang, Stephan; Whiteside, Theresa L.

2011-01-01

Objective The ectonucleotidase CD39 is an enzyme involved in adenosine production. Its surface expression on human regulatory T cells (Treg) allows for their flow-cytometry-based isolation from peripheral blood. To further develop and improve this method on a scale supporting translational studies, we introduced capture of CD39+ Treg on magnetic immunobeads. Methods Peripheral blood mononuclear cells (PBMC) obtained from healthy donors were used for negative selection of CD4+ T cells on AutoMACS using antibodies (Abs) specific for all lineage+ cells. CD4+CD39+ Treg were captured by biotin-conjugated anti-CD39 Abs and anti-biotin Ab-coated magnetic beads. Isolated CD4+CD39+ T cells were phenotyped by flow cytometry for Treg-associated markers: CD39, CD73, FOXP3, CD25, CTLA-4, CCR4, CD45RO and CD121a or for the absence of CD127 and CD49d. CFSE-based proliferation assays and ATP hydrolysis were used to measure Treg functions. Results The purity, recovery and viability of the separated CD4+CD39+ T cells were satisfactory. The isolated CD4+CD39+ T cell population consisted of FOXP3+CD25+ T cells which hydrolyzed exogenous ATP and suppressed autologous CD4+ T cell proliferation and of FOXP3negCD25neg T cells without suppressor function. The same two subsets were detectable by flow cytometry in normal PBMC, gating on CD4+CD39+, CD4+CD127neg, CD4+CD49dneg or CD4+CD25high Treg. Conclusion CD4+CD39+ Treg capture on immunobeads led to a discovery of two CD39+ subsets. Similar to CD39+ Treg in the peripheral blood, half of these cells are CD25+FOXP3+ active suppressor cells, while the other half are CD25negFOXP3neg and do not mediate suppression. PMID:21513715

Expression of transient receptor potential vanilloid 1 (TRPV1) and 2 (TRPV2) in human peripheral blood.

PubMed

Saunders, Cassandra Im; Kunde, Dale A; Crawford, Amanda; Geraghty, Dominic P

2007-02-01

The vanilloid receptor family of cation channels includes the capsaicin-sensitive, proton- and heat-activated TRPV1 and noxious heat-activated TRPV2. The present study demonstrates both gene and protein expression of TRPV1 and TRPV2 in human peripheral blood cells (PBCs) using molecular and immunocytochemical techniques. Using reverse-transcription polymerase chain reaction (RT-PCR) and quantitative real-time RT-PCR (qRT-PCR), TRPV1 and TRPV2 mRNA was detected in mRNA isolated from human whole peripheral blood. Using qRT-PCR, TRPV2 mRNA was highly expressed in human whole blood isolates (9.33+/-1.19 x 10(4)copies per 10(6)copies of the housekeeping gene GAPDH), whereas TRPV1 message was detected at approximately 150-fold lower levels (638+/-121 copies per 10(6)copies GAPDH). At the protein level, TRPV1 and TRPV2 activity was determined immunocytochemically in a lymphocyte-enriched mononuclear cell preparation (83+/-2% lymphocytes). Cells were labelled with rabbit anti-TRPV1 or goat anti-TRPV2 (1:500) and subsequently labelled with goat Texas red- (TRPV1) or FITC-(TRPV2) conjugated secondary antibodies (1:1000). All cells demonstrated punctate TRPV1-immunoreactivity, which appeared to be on the plasma membrane and in the cytoplasm. In contrast, cells within subjects appeared to express the TRPV1 protein at varying intensities. TRPV2-immunoreactivity appeared diffuse. This is the first study to demonstrate the presence of both TRPV1 and TRPV2 in human peripheral lymphocytes. Further studies need to be undertaken in order to determine the role of TRPV channels in these cells.

Peripheral KV7 channels regulate visceral sensory function in mouse and human colon

PubMed Central

Hockley, James RF; Reed, David E; Smith, Ewan St. John; Bulmer, David C; Blackshaw, L Ashley

2017-01-01

Background Chronic visceral pain is a defining symptom of many gastrointestinal disorders. The KV7 family (KV7.1–KV7.5) of voltage-gated potassium channels mediates the M current that regulates excitability in peripheral sensory nociceptors and central pain pathways. Here, we use a combination of immunohistochemistry, gut-nerve electrophysiological recordings in both mouse and human tissues, and single-cell qualitative real-time polymerase chain reaction of gut-projecting sensory neurons, to investigate the contribution of peripheral KV7 channels to visceral nociception. Results Immunohistochemical staining of mouse colon revealed labelling of KV7 subtypes (KV7.3 and KV7.5) with CGRP around intrinsic enteric neurons of the myenteric plexuses and within extrinsic sensory fibres along mesenteric blood vessels. Treatment with the KV7 opener retigabine almost completely abolished visceral afferent firing evoked by the algogen bradykinin, in agreement with significant co-expression of mRNA transcripts by single-cell qualitative real-time polymerase chain reaction for KCNQ subtypes and the B2 bradykinin receptor in retrogradely labelled extrinsic sensory neurons from the colon. Retigabine also attenuated responses to mechanical stimulation of the bowel following noxious distension (0–80 mmHg) in a concentration-dependent manner, whereas the KV7 blocker XE991 potentiated such responses. In human bowel tissues, KV7.3 and KV7.5 were expressed in neuronal varicosities co-labelled with synaptophysin and CGRP, and retigabine inhibited bradykinin-induced afferent activation in afferent recordings from human colon. Conclusions We show that KV7 channels contribute to the sensitivity of visceral sensory neurons to noxious chemical and mechanical stimuli in both mouse and human gut tissues. As such, peripherally restricted KV7 openers may represent a viable therapeutic modality for the treatment of gastrointestinal pathologies. PMID:28566000

Concurrent detection of secreted products from human lymphocytes by microengraving: cytokines and antigen-reactive antibodies

PubMed Central

Bradshaw, Elizabeth M.; Kent, Sally C.; Tripuraneni, Vinay; Orban, Tihamer; Ploegh, Hidde L.; Hafler, David A.; Love, J. Christopher

2008-01-01

Cell surface determinants, cytokines and antibodies secreted by hematopoietic cells are used to classify their lineage and function. Currently available techniques are unable to elucidate multiple secreted proteins while also assigning phenotypic surface-displayed markers to the individual living cells. Here, a soft lithographic method, microengraving, was adapted for the multiplexed interrogation of populations of individual human peripheral blood mononuclear cells for secreted cytokines (IFN-γ and IL-6), antigen-specific antibodies, and lineage-specific surface-expressed markers. Application of the method to a clinical sample from a recent onset Type 1 diabetic subject with a positive titer of anti-insulin antibodies showed that ~0.58% of circulating CD19+ B cells secreted proinsulin-reactive antibodies of the IgG isotype and 2–3% of circulating cells secreted IL-6. These data demonstrate the utility of microengraving for interrogating multiple phenotypes of single human cells concurrently and for detecting rare populations of cells by their secreted products. PMID:18675591

Diversity and human perceptions of bees (Hymenoptera: Apoidea) in Southeast Asian megacities.

PubMed

Sing, Kong-Wah; Wang, Wen-Zhi; Wan, Tao; Lee, Ping-Shin; Li, Zong-Xu; Chen, Xing; Wang, Yun-Yu; Wilson, John-James

2016-10-01

Urbanization requires the conversion of natural land cover to cover with human-constructed elements and is considered a major threat to biodiversity. Bee populations, globally, are under threat; however, the effect of rapid urban expansion in Southeast Asia on bee diversity has not been investigated. Given the pressing issues of bee conservation and urbanization in Southeast Asia, coupled with complex factors surrounding human-bee coexistence, we investigated bee diversity and human perceptions of bees in four megacities. We sampled bees and conducted questionnaires at three different site types in each megacity: a botanical garden, central business district, and peripheral suburban areas. Overall, the mean species richness and abundance of bees were significantly higher in peripheral suburban areas than central business districts; however, there were no significant differences in the mean species richness and abundance between botanical gardens and peripheral suburban areas or botanical gardens and central business districts. Urban residents were unlikely to have seen bees but agreed that bees have a right to exist in their natural environment. Residents who did notice and interact with bees, even though being stung, were more likely to have positive opinions towards the presence of bees in cities.

THE REGULATION ROLE OF CAROTID BODY PERIPHERAL CHEMORECEPTORS IN PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL CONDITIONS.

PubMed

Lazovic, Biljana; Zlatkovic Svenda, Mirjana; Durmic, Tijana; Stajic, Zoran; Duric, Vesna; Zugic, Vladimir

2016-11-01

The major oxygen sensors in the human body are peripheral chemoreceptors. also known as interoreceptors- as connected with internal organs, located in the aortic arch and in the body of the common carotid artery. Chemoreceptor function under physiological conditions. Stimulation of peripheral chemoreceptors during enviromental hypoxia causes a reflex-mediated increased ventilation, followed by the increase of the muscle sympatic activity, aiming to maintain tissue oxygen homeostatis, as well as glucosae, homeostatis. Besides that, peripheral chemoreceptors interact with central chemoreceptors. responsible for carbon dioxide changes . and they are able to modulate each other. Chemoreceptor function in pathophysiological conditions. Investigations of respiratory function in many pathological processes, such as hypertension, obstructive sleep apnea, congestive heart failure and many other diseases that are presented with enhanced peripheral chemosensitivity and impaired functional sy mpatholysis ultimately determine the peripheral chemorcceptor role and significance of peripheral chemoreceptors in the process of those pathological conditions development. Considering this, the presumed influence of peripheral chemoreceptors is important in patients having the above mentioned pathology. The importance and the role of peripheral chemoreceptors in the course of the breathing control is still controversial, despite many scientific attempts to solve this problem. The main objective of this review is to give the latest data on the peripheral chemoreceptor role and to highlight the importance of peripheral chemoreceptors for maintaining of oxygen homeostasis in pateints with hypoxia caused by either physiological or pathological conditions.

Diabetic peripheral neuropathy, is it an autoimmune disease?

PubMed

Janahi, Noor M; Santos, Derek; Blyth, Christine; Bakhiet, Moiz; Ellis, Mairghread

2015-11-01

Autoimmunity has been identified in a significant number of neuropathies, such as, proximal neuropathies, and autonomic neuropathies associated with diabetes mellitus. However, possible correlations between diabetic peripheral neuropathy and autoimmunity have not yet been fully investigated. This study was conducted to investigate whether autoimmunity is associated with the pathogenesis of human diabetic peripheral neuropathy. A case-control analysis included three groups: 30 patients with diabetic peripheral neuropathy, 30 diabetic control patients without neuropathy, and 30 healthy controls. Blood analysis was conducted to compare the percentages of positive antinuclear antibodies (ANA) between the three groups. Secondary analysis investigated the correlations between the presence of autoimmune antibodies and sample demographics and neurological manifestations. This research was considered as a pilot study encouraging further investigations to take place in the near future. Antinuclear antibodies were significantly present in the blood serum of patients with diabetic peripheral neuropathy in comparison to the control groups (p<0.001). The odds of positive values of ANA in the neuropathy group were 50 times higher when compared to control groups. Secondary analysis showed a significant correlation between the presence of ANA and the neurological manifestation of neuropathy (Neuropathy symptom score, Neuropathy disability score and Vibration Perception Threshold). The study demonstrated for the first time that human peripheral diabetic neuropathy may have an autoimmune aetiology. The new pathogenic factors may lead to the consideration of new management plans involving new therapeutic approaches and disease markers. Copyright © 2015 Elsevier B.V. All rights reserved.

Direct Conversion of Human Fibroblasts into Schwann Cells that Facilitate Regeneration of Injured Peripheral Nerve In Vivo.

PubMed

Sowa, Yoshihiro; Kishida, Tsunao; Tomita, Koichi; Yamamoto, Kenta; Numajiri, Toshiaki; Mazda, Osam

2017-04-01

Schwann cells (SCs) play pivotal roles in the maintenance and regeneration of the peripheral nervous system. Although transplantation of SCs enhances repair of experimentally damaged peripheral and central nerve tissues, it is difficult to prepare a sufficient number of functional SCs for transplantation therapy without causing adverse events for the donor. Here, we generated functional SCs by somatic cell reprogramming procedures and demonstrated their capability to promote peripheral nerve regeneration. Normal human fibroblasts were phenotypically converted into SCs by transducing SOX10 and Krox20 genes followed by culturing for 10 days resulting in approximately 43% directly converted Schwann cells (dSCs). The dSCs expressed SC-specific proteins, secreted neurotrophic factors, and induced neuronal cells to extend neurites. The dSCs also displayed myelin-forming capability both in vitro and in vivo. Moreover, transplantation of the dSCs into the transected sciatic nerve in mice resulted in significantly accelerated regeneration of the nerve and in improved motor function at a level comparable to that with transplantation of the SCs obtained from a peripheral nerve. The dSCs induced by our procedure may be applicable for novel regeneration therapy for not only peripheral nerve injury but also for central nerve damage and for neurodegenerative disorders related to SC dysfunction. Stem Cells Translational Medicine 2017;6:1207-1216. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Myeloid-derived suppressor cells can be efficiently generated from human hematopoietic progenitors and peripheral blood monocytes.

PubMed

Casacuberta-Serra, Sílvia; Parés, Marta; Golbano, Arantxa; Coves, Elisabet; Espejo, Carmen; Barquinero, Jordi

2017-07-01

Myeloid-derived suppressor cells (MDSCs) have an important role in controlling inflammation. As such, they are both a therapeutic target and, based on the administration of ex vivo-generated MDSCs, a therapeutic tool. However, there are relatively few reports describing methods to generate human MDSCs, and most of them rely on cells obtained from peripheral blood monocytes. We investigated alternative approaches to the generation of MDSCs from hematopoietic progenitors and monocytes. Purified CD34 + hematopoietic progenitors from apheresis products and CD14 + cells isolated from buffy coats were cultured in the presence of different combinations of cytokines. The resulting myeloid cell populations were then characterized phenotypically and functionally. Progenitor cells cultured in the presence of SCF+TPO+FLT3-L+GM-CSF+IL-6 gave rise to both monocytic (M)- and granulocytic (G)-MDSCs but production of the latter was partially inhibited by IL-3. M-MDSCs but not G-MDSCs were obtained by culturing peripheral blood monocytes with GM-CSF+IL-6 or GM-CSF+TGF-β1 for 6 days. CD14 expression was downregulated in the cultured cells. PD-L1 expression at baseline was lower in hematopoietic progenitor cell-derived than in monocyte-derived MDSCs, but was markedly increased in response to stimulation with LPS+IFN-γ. The functionality of the two MDSC subtypes was confirmed in studies of the suppression of allogeneic and mitogen-induced proliferation and by cytokine profiling. Here we describe both the culture conditions that allow the generation of MDSCs and the phenotypical and functional characterization of these cell populations.

Performance evaluation of 4 measuring methods of ground-glass opacities for predicting the 5-year relapse-free survival of patients with peripheral nonsmall cell lung cancer: a multicenter study.

PubMed

Kakinuma, Ryutaro; Kodama, Ken; Yamada, Kouzo; Yokoyama, Akira; Adachi, Shuji; Mori, Kiyoshi; Fukuyama, Yasuro; Fukuda, Yasuro; Kuriyama, Keiko; Oda, Junichi; Oda, Junji; Noguchi, Masayuki; Matsuno, Yoshihiro; Yokose, Tomoyuki; Ohmatsu, Hironobu; Nishiwaki, Yutaka

2008-01-01

To evaluate the performance of 4 methods of measuring the extent of ground-glass opacities as a means of predicting the 5-year relapse-free survival of patients with peripheral nonsmall cell lung cancer (NSLC). Ground-glass opacities on thin-section computed tomographic images of 120 peripheral NSLCs were measured at 7 medical institutions by the length, area, modified length, and vanishing ratio (VR) methods. The performance (Az) of each method in predicting the 5-year relapse-free survival was evaluated using receiver operating characteristic analysis. The mean Az value obtained by the length, area, modified length, and VR methods in the receiver operating characteristic analyses was 0.683, 0.702, 0.728, and 0.784, respectively. The differences between the mean Az value obtained by the VR method and by the other 3 methods were significant. Vanishing ratio method was the most accurate predictor of the 5-year relapse-free survival of patients with peripheral NSLC.

Effects of oral eicosapentaenoic acid versus docosahexaenoic acid on human peripheral blood mononuclear cell gene expression

USDA-ARS?s Scientific Manuscript database

Objective: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have beneficial effects on inflammation and cardiovascular disease (CVD). Our aim was to assess the effect of a six-week supplementation with either olive oil, EPA, or DHA on gene expression in peripheral blood mononuclear cells (...

The effect of interleukin-2 on canine peripheral nerve sheath tumours after marginal surgical excision: a double-blind randomized study

PubMed Central

2013-01-01

Background The objective of this study was to evaluate the effect on outcomes of intraoperative recombinant human interleukin-2 injection after surgical resection of peripheral nerve sheath tumours. In this double-blind trial, 40 patients due to undergo surgical excision (<5 mm margins) of presumed peripheral nerve sheath tumours were randomized to receive intraoperative injection of interleukin-2 or placebo into the wound bed. Results There were no significant differences in any variable investigated or in median survival between the two groups. The median recurrence free interval was 874 days (range 48–2141 days), The recurrence-free interval and overall survival time were significantly longer in dogs that undergone the primary surgery by a specialist-certified surgeon compared to a referring veterinarian regardless of whether additional adjunct therapy was given. Conclusion Overall, marginal excision of peripheral nerve sheath tumours in dogs resulted in a long survival time, but adjuvant treatment with recombinant human interleukin-2 (rhIL-2) did not provide a survival advantage. PMID:23927575

The role of the amygdala and the basal ganglia in visual processing of central vs. peripheral emotional content.

PubMed

Almeida, Inês; van Asselen, Marieke; Castelo-Branco, Miguel

2013-09-01

In human cognition, most relevant stimuli, such as faces, are processed in central vision. However, it is widely believed that recognition of relevant stimuli (e.g. threatening animal faces) at peripheral locations is also important due to their survival value. Moreover, task instructions have been shown to modulate brain regions involved in threat recognition (e.g. the amygdala). In this respect it is also controversial whether tasks requiring explicit focus on stimulus threat content vs. implicit processing differently engage primitive subcortical structures involved in emotional appraisal. Here we have addressed the role of central vs. peripheral processing in the human amygdala using animal threatening vs. non-threatening face stimuli. First, a simple animal face recognition task with threatening and non-threatening animal faces, as well as non-face control stimuli, was employed in naïve subjects (implicit task). A subsequent task was then performed with the same stimulus categories (but different stimuli) in which subjects were told to explicitly detect threat signals. We found lateralized amygdala responses both to the spatial location of stimuli and to the threatening content of faces depending on the task performed: the right amygdala showed increased responses to central compared to left presented stimuli specifically during the threat detection task, while the left amygdala was better prone to discriminate threatening faces from non-facial displays during the animal face recognition task. Additionally, the right amygdala responded to faces during the threat detection task but only when centrally presented. Moreover, we have found no evidence for superior responses of the amygdala to peripheral stimuli. Importantly, we have found that striatal regions activate differentially depending on peripheral vs. central processing of threatening faces. Accordingly, peripheral processing of these stimuli activated more strongly the putaminal region, while central processing engaged mainly the caudate nucleus. We conclude that the human amygdala has a central bias for face stimuli, and that visual processing recruits different striatal regions, putaminal or caudate based, depending on the task and on whether peripheral or central visual processing is involved. © 2013 Elsevier Ltd. All rights reserved.

Methods for the detection of antioxidants which prevent age related diseases: a critical review with particular emphasis on human intervention studies.

PubMed

Hoelzl, C; Bichler, J; Ferk, F; Simic, T; Nersesyan, A; Elbling, L; Ehrlich, V; Chakraborty, A; Knasmüller, S

2005-03-01

It is well documented that reactive oxygen species (ROS) are involved in the aetiology of age related diseases. Over the last decades, strong efforts have been made to identify antioxidants in human foods and numerous promising compounds have been detected which are used for the production of supplements and functional foods. The present paper describes the advantages and limitations of methods which are currently used for the identification of antioxidants. Numerous in vitro methods are available which are easy to perform and largely used in screening trials. However, the results of such tests are only partly relevant for humans as certain active compounds (e.g. those with large molecular configuration) are only poorly absorbed in the gastrointestinal tract and/or may undergo metabolic degradation. Therefore experimental models are required which provide information if protective effects take place in humans under realistic conditions. Over the last years, several methods have been developed which are increasingly used in human intervention trials. The most widely used techniques are chemical determinations of oxidised guanosine in peripheral blood cells or urine and single cell gel electrophoresis (comet) assays with lymphocytes which are based on the measurement of DNA migration in an electric field. By using of DNA-restriction enzymes (formamidopyrimidine DNA glycosylase and endonuclease III) it is possible to monitor the endogenous formation of oxidised purines and pyrimidines; recently also protocols have been developed which enable to monitor alterations in the repair of oxidised DNA. Alternatively, also the frequency of micronucleated cells can be monitored with the cytokinesis block method in peripheral human blood cells before and after intervention with putative antioxidants. To obtain information on alterations of the sensitivity towards oxidative damage, the cells can be treated ex vivo with ROS (H(2)O(2) exposure, radiation). The evaluation of currently available human studies shows that in approximately half of them protective effects of dietary factors towards oxidative DNA-damage were observed. Earlier studies focused predominantly on the effects of vitamins (A, C, E) and carotenoids, more recently also the effects of fruit juices (from grapes, kiwi) and beverages (soy milk, tea, coffee), vegetables (tomato products, berries, Brussels sprouts) and other components of the human diet (coenzyme Q(10), polyunsaturated fatty acids) were investigated. On the basis of the results of these studies it was possible to identify dietary compounds which are highly active (e.g. gallic acid). At present, strong efforts are made to elucidate whether the different parameters of oxidative DNA-damage correlates with life span, cancer and other age related diseases. The new techniques are highly useful tools which provide valuable information if dietary components cause antioxidant effects in humans and can be used to identify individual protective compounds and also to develop nutritional strategies to reduce the adverse health effects of ROS.

Cellular uptake of polymeric nanocapsules loaded with ICG by human blood monocytes and human spleen macrophages

NASA Astrophysics Data System (ADS)

Bahmani, Baharak; Jung, Bongsu; Gupta, Sharad; Anvari, Bahman

2010-02-01

Indocyanine green (ICG) is an FDA approved near infrared dye used in assessment of hepatic function and ophthalmological vascular imaging. However, given the rapid clearance of ICG from the blood stream, its imaging and phototherapeutic applications remain very limited. As a potential method to increase circulation time of ICG, and extend its clinical applications, we have encapsulated ICG within polymeric based nanoconstructs whose surface can be coated with various materials including polyethylene glycol (PEG). To gain an understanding of the interaction between ICG-containing nanocapsules (ICG-NCs) and vascular cells, we are characterizing the uptake of the nanocapsules coated with various materials by human peripheral blood monocytes and human spleen macrophages using fluorescence microscopy. Results of these studies will be useful in identifying the appropriate coating material that will result in increased circulation time of ICG-NCs within the vasculature.

Expression of extracellular calcium (Ca2+o)-sensing receptor in human peripheral blood monocytes

NASA Technical Reports Server (NTRS)

Yamaguchi, T.; Olozak, I.; Chattopadhyay, N.; Butters, R. R.; Kifor, O.; Scadden, D. T.; Brown, E. M.; O'Malley, B. W. (Principal Investigator)

1998-01-01

The calcium-sensing receptor (CaR) is a G protein-coupled receptor playing key roles in extracellular calcium ion (Ca2+o) homeostasis in parathyroid gland and kidney. Macrophage-like mononuclear cells appear at sites of osteoclastic bone resorption during bone turnover and may play a role in the "reversal" phase of skeletal remodeling that follows osteoclastic resorption and precedes osteoblastic bone formation. Bone resorption produces substantial local increases in Ca2+o that could provide a signal for such mononuclear cells present locally within the bone marrow microenvironment. Indeed, previous studies by other investigators have shown that raising Ca2+o either in vivo or in vitro stimulated the release of interleukin-6 (IL-6) from human peripheral blood monocytes, suggesting that these cells express a Ca2+o-sensing mechanism. In these earlier studies, however, the use of reverse transcription-polymerase chain reaction (RT-PCR) failed to detect transcripts for the CaR previously cloned from parathyroid and kidney in peripheral blood monocytes. Since we recently found that non-specific esterase-positive, putative monocytes isolated from murine bone marrow express the CaR, we reevaluated the expression of this receptor in human peripheral blood monocytes. Immunocytochemistry, flow cytometry, and Western blot analysis, performed using a polyclonal antiserum specific for the CaR, detected CaR protein in human monocytes. In addition, the use of RT-PCR with CaR-specific primers, followed by nucleotide sequencing of the amplified products, identified CaR transcripts in the cells. Therefore, taken together, our data show that human peripheral blood monocytes possess both CaR protein and mRNA very similar if not identical to those expressed in parathyroid and kidney that could mediate the previously described, direct effects of Ca2+o on these cells. Furthermore, since mononuclear cells isolated from bone marrow also express the CaR, the latter might play some role in the "reversal" phase of bone remodeling, sensing local changes in Ca2+o resulting from osteoclastic bone resorption and secreting osteotropic cytokines or performing other Ca2+o-regulated functions that contribute to the control of bone turnover.

IL‐12 and IL‐15 induce the expression of CXCR6 and CD49a on peripheral natural killer cells

PubMed Central

Hydes, Theresa; Noll, Angela; Salinas‐Riester, Gabriela; Abuhilal, Mohammed; Armstrong, Thomas; Hamady, Zaed; Primrose, John; Takhar, Arjun; Walter, Lutz

2017-01-01

Abstract Introduction Murine hepatic NK cells exhibit adaptive features, with liver‐specific adhesion molecules CXCR6 and CD49a acting as surface markers. Methods We investigated human liver‐resident CXCR6+ and CD49a+ NK cells using RNA sequencing, flow cytometry, and functional analysis. We further assessed the role of cytokines in generating NK cells with these phenotypes from the peripheral blood. Results Hepatic CD49a+ NK cells could be induced using cytokines and produce high quantities of IFNγ and TNFα, in contrast to hepatic CXCR6+ NK cells. RNA sequencing of liver‐resident CXCR6+ NK cells confirmed a tolerant immature phenotype with reduced expression of markers associated with maturity and cytotoxicity. Liver‐resident double‐positive CXCR6 + CD49a+ hepatic NK cells are immature but maintain high expression of Th1 cytokines as observed for single‐positive CD49a+ NK cells. We show that stimulation with activating cytokines can readily induce upregulation of both CD49a and CXCR6 on NK cells in the peripheral blood. In particular, IL‐12 and IL‐15 can generate CXCR6 + CD49a+ NK cells in vitro from NK cells isolated from the peripheral blood, with comparable phenotypic and functional features to liver‐resident CD49a+ NK cells, including enhanced IFNγ and NKG2C expression. Conclusion IL‐12 and IL‐15 may be key for generating NK cells with a tissue‐homing phenotype and strong Th1 cytokine profile in the blood, and links peripheral activation of NK cells with tissue‐homing. These findings may have important therapeutic implications for immunotherapy of chronic liver disease. PMID:28952190

Electron microscopy of human peripheral nerves of clinical relevance to the practice of nerve blocks. A structural and ultrastructural review based on original experimental and laboratory data.

PubMed

Reina, M A; Arriazu, R; Collier, C B; Sala-Blanch, X; Izquierdo, L; de Andrés, J

2013-12-01

The goal is to describe the ultrastructure of normal human peripheral nerves, and to highlight key aspects that are relevant to the practice of peripheral nerve block anaesthesia. Using samples of sciatic nerve obtained from patients, and dural sac, nerve root cuff and brachial plexus dissected from fresh human cadavers, an analysis of the structure of peripheral nerve axons and distribution of fascicles and topographic composition of the layers that cover the nerve is presented. Myelinated and unmyelinated axons, fascicles, epineurium, perineurium and endoneurium obtained from patients and fresh cadavers were studied by light microscopy using immunohistochemical techniques, and transmission and scanning electron microscopy. Structure of perineurium and intrafascicular capillaries, and its implications in blood-nerve barrier were revised. Each of the anatomical elements is analyzed individually with regard to its relevance to clinical practice to regional anaesthesia. Routine practice of regional anaesthetic techniques and ultrasound identification of nerve structures has led to conceptions, which repercussions may be relevant in future applications of these techniques. In this regard, the ultrastructural and histological perspective accomplished through findings of this study aims at enlightening arising questions within the field of regional anaesthesia. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

Evaluation of radiation necrosis and malignant glioma in rat models using diffusion tensor MR imaging

PubMed Central

Wang, Silun; Chen, Yifei; Lal, Bachchu; Ford, Eric; Tryggestad, Erik; Armour, Michael; Yan, Kun; Laterra, John; Zhou, Jinyuan

2011-01-01

Standard MRI cannot distinguish between radiation necrosis and tumor progression; however, this distinction is critical in the assessment of tumor response to therapy. In this study, one delayed radiation necrosis model (dose, 40 Gy; radiation field, 10 × 10 mm2; n = 13) and two orthotopic glioma models in rats (9L gliosarcoma, n = 8; human glioma xenografts, n = 5) were compared using multiple DTI indices. A visible isotropic apparent diffusion coefficient (ADC) pattern was observed in the lesion due to radiation necrosis, which consisted of a hypointense central zone and a hyperintense peripheral zone. There were significantly lower ADC, parallel diffusivity, and perpendicular diffusivity in the necrotic central zone than in the peripheral zone (all p < 0.001). When radiation-induced necrosis was compared with viable tumor, radiation necrosis had significantly lower ADC than 9L gliosarcoma and human glioma xenografts (both p < 0.01) in the central zone, and significantly lower FA than 9L gliosarcoma (p = 0.005) and human glioma xenografts (p = 0.012) in the peripheral zone. Histological analysis revealed parenchymal coagulative necrosis in the central zone, and damaged vessels and reactive astrogliosis in the peripheral zone. These data suggest that qualitative and quantitative analysis of the DTI maps can provide useful information by which to distinguish between radiation necrosis and viable glioma. PMID:21948114

Phenotypic and Functional Characterization of Peripheral Blood Lymphocytes from Various Age- and Sex-Specific Groups of Owl Monkeys (Aotus nancymaae).

PubMed

Nehete, Pramod N; Nehete, Bharti P; Chitta, Sriram; Williams, Lawrence E; Abee, Christian R

2017-02-01

Owl monkeys (Aotus nancymaae) are New World NHP that serve an important role in vaccine development and as a model for human disease conditions such as malaria. Despite the past contributions of this animal model, limited information is available about the phenotype and functional properties of peripheral blood lymphocytes in reference to sex and age. Using a panel of human antibodies and a set of standardized human immune assays, we identified and characterized various peripheral blood lymphocyte subsets, evaluated the immune functions of T cells, and analyzed cytokines relative to sex and age in healthy owl monkeys. We noted age- and sex-dependent changes in CD28+ (an essential T cell costimulatory molecule) and CD95+ (an apoptotic surface marker) T cells and various levels of cytokines in the plasma. In immune assays of freshly isolated peripheral blood mononuclear cells, IFNγ and perforin responses were significantly higher in female than in male monkeys and in young adults than in juvenile and geriatric groups, despite similar lymphocyte (particularly T cell) populations in these groups. Our current findings may be useful in exploring Aotus monkeys as a model system for the study of aging, susceptibility to infectious diseases, and age-associated differences in vaccine efficacy, and other challenges particular to pediatric and geriatric patients.

Types of neural guides and using nanotechnology for peripheral nerve reconstruction

PubMed Central

Biazar, Esmaeil; Khorasani, MT; Montazeri, Naser; Pourshamsian, Khalil; Daliri, Morteza; T, Mostafa Rezaei; B, Mahmoud Jabarvand; Khoshzaban, Ahad; K, Saeed Heidari; Jafarpour, Mostafa; Roviemiab, Ziba

2010-01-01

Peripheral nerve injuries can lead to lifetime loss of function and permanent disfigurement. Different methods, such as conventional allograft procedures and use of biologic tubes present problems when used for damaged peripheral nerve reconstruction. Designed scaffolds comprised of natural and synthetic materials are now widely used in the reconstruction of damaged tissues. Utilization of absorbable and nonabsorbable synthetic and natural polymers with unique characteristics can be an appropriate solution to repair damaged nerve tissues. Polymeric nanofibrous scaffolds with properties similar to neural structures can be more effective in the reconstruction process. Better cell adhesion and migration, more guiding of axons, and structural features, such as porosity, provide a clearer role for nanofibers in the restoration of neural tissues. In this paper, basic concepts of peripheral nerve injury, types of artificial and natural guides, and methods to improve the performance of tubes, such as orientation, nanotechnology applications for nerve reconstruction, fibers and nanofibers, electrospinning methods, and their application in peripheral nerve reconstruction are reviewed. PMID:21042546

Peripheral refraction in normal infant rhesus monkeys

PubMed Central

Hung, Li-Fang; Ramamirtham, Ramkumar; Huang, Juan; Qiao-Grider, Ying; Smith, Earl L.

2008-01-01

Purpose To characterize peripheral refractions in infant monkeys. Methods Cross-sectional data for horizontal refractions were obtained from 58 normal rhesus monkeys at 3 weeks of age. Longitudinal data were obtained for both the vertical and horizontal meridians from 17 monkeys. Refractive errors were measured by retinoscopy along the pupillary axis and at eccentricities of 15, 30, and 45 degrees. Axial dimensions and corneal power were measured by ultrasonography and keratometry, respectively. Results In infant monkeys, the degree of radial astigmatism increased symmetrically with eccentricity in all meridians. There were, however, initial nasal-temporal and superior-inferior asymmetries in the spherical-equivalent refractive errors. Specifically, the refractions in the temporal and superior fields were similar to the central ametropia, but the refractions in the nasal and inferior fields were more myopic than the central ametropia and the relative nasal field myopia increased with the degree of central hyperopia. With age, the degree of radial astigmatism decreased in all meridians and the refractions became more symmetrical along both the horizontal and vertical meridians; small degrees of relative myopia were evident in all fields. Conclusions As in adult humans, refractive error varied as a function of eccentricity in infant monkeys and the pattern of peripheral refraction varied with the central refractive error. With age, emmetropization occurred for both central and peripheral refractive errors resulting in similar refractions across the central 45 degrees of the visual field, which may reflect the actions of vision-dependent, growth-control mechanisms operating over a wide area of the posterior globe. PMID:18487366

Chronic inorganic arsenic exposure in vitro induces a cancer cell phenotype in human peripheral lung epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Person, Rachel J.; Olive Ngalame, Ntube N.; Makia, Ngome L.

Inorganic arsenic is a human lung carcinogen. We studied the ability of chronic inorganic arsenic (2 μM; as sodium arsenite) exposure to induce a cancer phenotype in the immortalized, non-tumorigenic human lung peripheral epithelial cell line, HPL-1D. After 38 weeks of continuous arsenic exposure, secreted matrix metalloproteinase-2 (MMP2) activity increased to over 200% of control, levels linked to arsenic-induced cancer phenotypes in other cell lines. The invasive capacity of these chronic arsenic-treated lung epithelial (CATLE) cells increased to 320% of control and colony formation increased to 280% of control. CATLE cells showed enhanced proliferation in serum-free media indicative of autonomousmore » growth. Compared to control cells, CATLE cells showed reduced protein expression of the tumor suppressor gene PTEN (decreased to 26% of control) and the putative tumor suppressor gene SLC38A3 (14% of control). Morphological evidence of epithelial-to-mesenchymal transition (EMT) occurred in CATLE cells together with appropriate changes in expression of the EMT markers vimentin (VIM; increased to 300% of control) and e-cadherin (CDH1; decreased to 16% of control). EMT is common in carcinogenic transformation of epithelial cells. CATLE cells showed increased KRAS (291%), ERK1/2 (274%), phosphorylated ERK (p-ERK; 152%), and phosphorylated AKT1 (p-AKT1; 170%) protein expression. Increased transcript expression of metallothioneins, MT1A and MT2A and the stress response genes HMOX1 (690%) and HIF1A (247%) occurred in CATLE cells possibly in adaptation to chronic arsenic exposure. Thus, arsenic induced multiple cancer cell characteristics in human peripheral lung epithelial cells. This model may be useful to assess mechanisms of arsenic-induced lung cancer. - Highlights: • Chronic arsenic exposure transforms a human peripheral lung epithelia cell line. • Cells acquire characteristics in common with human lung adenocarcinoma cells. • These transformed cells provide a valuable model for arsenic-induced lung cancer.« less

Activation of TrkB with TAM-163 Results in Opposite Effects on Body Weight in Rodents and Non-Human Primates

PubMed Central

Perreault, Mylène; Feng, Guo; Will, Sarah; Gareski, Tiffany; Kubasiak, David; Marquette, Kimberly; Vugmeyster, Yulia; Unger, Thaddeus J.; Jones, Juli; Qadri, Ariful; Hahm, Seung; Sun, Ying; Rohde, Cynthia M.; Zwijnenberg, Raphael; Paulsen, Janet; Gimeno, Ruth E.

2013-01-01

Strong genetic data link the Tyrosine kinase receptor B (TrkB) and its major endogenous ligand brain-derived neurotrophic factor (BDNF) to the regulation of energy homeostasis, with loss-of-function mutations in either gene causing severe obesity in both mice and humans. It has previously been reported that peripheral administration of the endogenous TrkB agonist ligand neurotrophin-4 (NT-4) profoundly decreases food intake and body weight in rodents, while paradoxically increasing these same parameters in monkeys. We generated a humanized TrkB agonist antibody, TAM-163, and characterized its therapeutic potential in several models of type 2 diabetes and obesity. In vitro, TAM-163 bound to human and rodent TrkB with high affinity, activated all aspects of the TrkB signaling cascade and induced TrkB internalization and degradation in a manner similar to BDNF. In vivo, peripheral administration of TAM-163 decreased food intake and/or body weight in mice, rats, hamsters, and dogs, but increased food intake and body weight in monkeys. The magnitude of weight change was similar in rodents and non-human primates, occurred at doses where there was no appreciable penetration into deep structures of the brain, and could not be explained by differences in exposures between species. Rather, peripherally administered TAM-163 localized to areas in the hypothalamus and the brain stem located outside the blood-brain barrier in a similar manner between rodents and non-human primates, suggesting differences in neuroanatomy across species. Our data demonstrate that a TrkB agonist antibody, administered peripherally, causes species-dependent effects on body weight similar to the endogenous TrkB ligand NT-4. The possible clinical utility of TrkB agonism in treating weight regulatory disorder, such as obesity or cachexia, will require evaluation in man. PMID:23700410

Novel, high-yield red blood cell production methods from CD34-positive cells derived from human embryonic stem, yolk sac, fetal liver, cord blood, and peripheral blood.

PubMed

Olivier, Emmanuel; Qiu, Caihong; Bouhassira, Eric E

2012-08-01

The current supply of red blood cells expressing rare blood groups is not sufficient to cover all the existing transfusion needs for chronically transfused patients, such as sickle cell disease homozygous carriers, because of alloimmunization. In vitro production of cultured red blood cells is slowly emerging as a possible complement to the existing collection-based red blood cell procurement system. The yield of cultured red blood cells can theoretically be maximized by amplifying the stem, progenitor, or precursor compartment. Here, we combined methods designed to expand these three compartments to optimize the yield of cultured red blood cells and found that exposing CD34(+) cells to a short pulse of cytokines favorable for erythroid differentiation prior to stem cell expansion followed by progenitor expansion produced the highest yield of erythroid cells. This novel serum-free red blood cell production protocol was efficient on CD34(+) cells derived from human embryonic stem cells, 6-8-week yolk sacs, 16-18-week fetal livers, cord blood, and peripheral blood. The yields of cells obtained with these new protocols were larger by an order of magnitude than the yields observed previously. Globin expression analysis by high-performance liquid chromatography revealed that these expansion protocols generally yielded red blood cells that expressed a globin profile similar to that expected for the developmental age of the CD34(+) cells.

Heat transfer unit and method for prefabricated vessel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tamburello, David A.; Kesterson, Matthew R; Hardy, Bruce J.

Vessel assemblies, heat transfer units for prefabricated vessels, and methods for heat transfer prefabricated vessel are provided. A heat transfer unit includes a central rod, and a plurality of peripheral rods surrounding the central rod and connected to the central rod. The plurality of peripheral rods are movable between a first collapsed position and a second bowed position, wherein in the second bowed position a midpoint of each of the plurality of peripheral rods is spaced from the central rod relative to in the first position. The heat transfer unit further includes a heat transfer element connected to one ofmore » the plurality of peripheral rods.« less

Angiotensin II type 2 receptor (AT2R) localization and antagonist-mediated inhibition of capsaicin responses and neurite outgrowth in human and rat sensory neurons

PubMed Central

Anand, U; Facer, P; Yiangou, Y; Sinisi, M; Fox, M; McCarthy, T; Bountra, C; Korchev, YE; Anand, P

2013-01-01

Background The angiotensin II (AngII) receptor subtype 2 (AT2R) is expressed in sensory neurons and may play a role in nociception and neuronal regeneration. Methods We used immunostaining with characterized antibodies to study the localization of AT2R in cultured human and rat dorsal root ganglion (DRG) neurons and a range of human tissues. The effects of AngII and AT2R antagonist EMA401 on capsaicin responses in cultured human and rat (DRG) neurons were measured with calcium imaging, on neurite length and density with Gap43 immunostaining, and on cyclic adenosine monophosphate (cAMP) expression using immunofluorescence. Results AT2R expression was localized in small-/medium-sized cultured neurons of human and rat DRG. Treatment with the AT2R antagonist EMA401 resulted in dose-related functional inhibition of capsaicin responses (IC50 = 10 nmol/L), which was reversed by 8-bromo-cAMP, and reduced neurite length and density; AngII treatment significantly enhanced capsaicin responses, cAMP levels and neurite outgrowth. The AT1R antagonist losartan had no effect on capsaicin responses. AT2R was localized in sensory neurons of human DRG, and nerve fibres in peripheral nerves, skin, urinary bladder and bowel. A majority sub-population (60%) of small-/medium-diameter neuronal cells were immunopositive in both control post-mortem and avulsion-injured human DRG; some very small neurons appeared to be intensely immunoreactive, with TRPV1 co-localization. While AT2R levels were reduced in human limb peripheral nerve segments proximal to injury, they were preserved in painful neuromas. Conclusions AT2R antagonists could be particularly useful in the treatment of chronic pain and hypersensitivity associated with abnormal nerve sprouting. PMID:23255326

Prevalence and variables associated with an abnormal ankle-brachial index among patients with human immunodeficiency virus/acquired immunodeficiency syndrome.

PubMed

Hinojosa, Carlos A; Nunez-Salgado, Ana E; Anaya-Ayala, Javier E; Laparra-Escareno, Hugo; Ortiz-Lopez, Laura J; Herrera-Caceres, Jaime O; Crabtree-Ramirez, Brenda E; Sierra-Madero, Juan G

2018-01-01

Objectives The longer survival of patients with human immunodeficiency virus/acquired immunodeficiency syndrome and the introduction of the highly active antiretroviral therapy have increased the number of chronic conditions; among these, cardiovascular diseases. The aim of this study is to determine patient, disease, and factors associated with peripheral arterial disease in a population of patients with human immunodeficiency virus/acquired immunodeficiency syndrome. Methods A prospective nested case-control study of a cohort of patients with human immunodeficiency virus/acquired immunodeficiency syndrome was conducted in a tertiary medical center in Mexico City. A sample size of 206 patients was calculated. Medical history, relevant laboratory data, peripheral arterial exam, and screening ankle-brachial index tests were obtained. Results The prevalence of abnormal ankle-brachial indexes was 20% (42 patients). Patient's mean age was 44 years ±13. The majority (98.5%) were actively receiving highly active antiretroviral therapy; active smoking was reported in 55 (27%), arterial hypertension and type 2 diabetes mellitus were found in 24 (12%) and 22 (11%) patients. Median time from the human immunodeficiency virus diagnosis was eight years (Interquartile range ±11); the mean CD4 count was 481, with a mean viral load of 13,557 copies (SD ± 69025.27) and 1889.18 (SD ± 9052.77) for patients with normal and abnormal ankle-brachial index and a median of 40 (IQ ± 2). Viral load ( p = 0.04) and number of years with human immunodeficiency virus/acquired immunodeficiency syndrome ( p = 0.04) were significantly associated with abnormal ankle-brachial indexes. Conclusions Abnormal ankle-brachial index seems to be more frequent in Mexican patients with human immunodeficiency virus/acquired immunodeficiency syndrome when compared with the general population at the same age. The most important factors associated with arterial disease were the viral load and the number of years with human immunodeficiency virus/acquired immunodeficiency syndrome. ClinicalTrials.gov NCT02264509.

A novel wide-field-of-view display method with higher central resolution for hyper-realistic head dome projector

NASA Astrophysics Data System (ADS)

Hotta, Aira; Sasaki, Takashi; Okumura, Haruhiko

2007-02-01

In this paper, we propose a novel display method to realize a high-resolution image in a central visual field for a hyper-realistic head dome projector. The method uses image processing based on the characteristics of human vision, namely, high central visual acuity and low peripheral visual acuity, and pixel shift technology, which is one of the resolution-enhancing technologies for projectors. The projected image with our method is a fine wide-viewing-angle image with high definition in the central visual field. We evaluated the psychological effects of the projected images with our method in terms of sensation of reality. According to the result, we obtained 1.5 times higher resolution in the central visual field and a greater sensation of reality by using our method.

Redundant Function of Plasmacytoid and Conventional Dendritic Cells Is Required To Survive a Natural Virus Infection.

PubMed

Kaminsky, Lauren W; Sei, Janet J; Parekh, Nikhil J; Davies, Michael L; Reider, Irene E; Krouse, Tracy E; Norbury, Christopher C

2015-10-01

Viruses that spread systemically from a peripheral site of infection cause morbidity and mortality in the human population. Innate myeloid cells, including monocytes, macrophages, monocyte-derived dendritic cells (mo-DC), and dendritic cells (DC), respond early during viral infection to control viral replication, reducing virus spread from the peripheral site. Ectromelia virus (ECTV), an orthopoxvirus that naturally infects the mouse, spreads systemically from the peripheral site of infection and results in death of susceptible mice. While phagocytic cells have a requisite role in the response to ECTV, the requirement for individual myeloid cell populations during acute immune responses to peripheral viral infection is unclear. In this study, a variety of myeloid-specific depletion methods were used to dissect the roles of individual myeloid cell subsets in the survival of ECTV infection. We showed that DC are the primary producers of type I interferons (T1-IFN), requisite cytokines for survival, following ECTV infection. DC, but not macrophages, monocytes, or granulocytes, were required for control of the virus and survival of mice following ECTV infection. Depletion of either plasmacytoid DC (pDC) alone or the lymphoid-resident DC subset (CD8α(+) DC) alone did not confer lethal susceptibility to ECTV. However, the function of at least one of the pDC or CD8α(+) DC subsets is required for survival of ECTV infection, as mice depleted of both populations were susceptible to ECTV challenge. The presence of at least one of these DC subsets is sufficient for cytokine production that reduces ECTV replication and virus spread, facilitating survival following infection. Prior to the eradication of variola virus, the orthopoxvirus that causes smallpox, one-third of infected people succumbed to the disease. Following successful eradication of smallpox, vaccination rates with the smallpox vaccine have significantly dropped. There is now an increasing incidence of zoonotic orthopoxvirus infections for which there are no effective treatments. Moreover, the safety of the smallpox vaccine is of great concern, as complications may arise, resulting in morbidity. Like many viruses that cause significant human diseases, orthopoxviruses spread from a peripheral site of infection to become systemic. This study elucidates the early requirement for innate immune cells in controlling a peripheral infection with ECTV, the causative agent of mousepox. We report that there is redundancy in the function of two innate immune cell subsets in controlling virus spread early during infection. The viral control mediated by these cell subsets presents a potential target for therapies and rational vaccine design. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

75 FR 56548 - Joint Meeting of the Peripheral and Central Nervous System Drugs Advisory Committee and the Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Joint Meeting of the Peripheral and Central Nervous System Drugs Advisory Committee and the Drug Safety... and Central Nervous System Drugs Advisory Committee and the Drug Safety and Risk Management Advisory...

Synthesis of antimicrobial silver nanoparticles through a photomediated reaction in an aqueous environment

PubMed Central

Banasiuk, Rafał; Frackowiak, Joanna E; Krychowiak, Marta; Matuszewska, Marta; Kawiak, Anna; Ziabka, Magdalena; Lendzion-Bielun, Zofia; Narajczyk, Magdalena; Krolicka, Aleksandra

2016-01-01

A fast, economical, and reproducible method for nanoparticle synthesis has been developed in our laboratory. The reaction is performed in an aqueous environment and utilizes light emitted by commercially available 1 W light-emitting diodes (λ =420 nm) as the catalyst. This method does not require nanoparticle seeds or toxic chemicals. The irradiation process is carried out for a period of up to 10 minutes, significantly reducing the time required for synthesis as well as environmental impact. By modulating various reaction parameters silver nanoparticles were obtained, which were predominantly either spherical or cubic. The produced nanoparticles demonstrated strong antimicrobial activity toward the examined bacterial strains. Additionally, testing the effect of silver nanoparticles on the human keratinocyte cell line and human peripheral blood mononuclear cells revealed that their cytotoxicity may be limited by modulating the employed concentrations of nanoparticles. PMID:26855570

On the use of Orbscan II to assess the peripheral corneal thickness in humans: a comparison with ultrasound pachometry measures.

PubMed

Jonuscheit, Sven; Doughty, Michael J; Button, Norman F

2007-03-01

To compare the measures of corneal thickness measurements obtained by an optical scanning slit method with those obtained by an ultrasound (US) pachometer, with special interest in the mid-peripheral (2.5 mm from centre) and peripheral (4.5 mm from centre) region of the cornea. Three measures of corneal thickness were taken using Orbscan II and then by US pachometry (under topical anaesthesia with benoxinate 0.4%) on 24 adults, aged 20-58 years and with up to 8.5 D of myopia. The full Orbscan topography maps were used to extract single point data along the horizontal corneal meridian for the geometric centre, 2.5 mm from centre (nasal and temporal) and 4.5 mm (nasal and temporal) from centre. No correction factor was used for the Orbscan data. The same set of measures were made with the US pachometer. In all cases, the averages of three (centre) or six (mid-periphery and periphery) readings were taken as the measurements from each cornea. Orbscan readings on the right eyes averaged 0.576, 0.632 and 0.712 mm for central, mid-peripheral and peripheral sites with average values for emmetropic subjects (<1 DS, n = 12) being marginally higher than for myopic subjects (average - 4.00 DS, n = 12). For US pachometry, the average values were however 0.522, 0.554 and 0.606 mm. Similar results were obtained on left eyes. Combining data from both eyes also showed that the mean difference between Orbscan II and US measures was not constant across the cornea, being 0.055 +/- 0.014 mm at the centre, 0.080 +/- 0.019 mm at mid-peripheral locations and 0.107 +/- 0.046 mm at the peripheral sites. These differences persisted after application of the generally recommended acoustic factor (x0.92) to all of the Orbscan readings. A single acoustic factor correction cannot be applied to all corneal thickness measures made with an Orbscan II to equate the measures to those made with an US pachometer.

[Human herpesvirus-6 pneumonitis following autologous peripheral blood stem cell transplantation].

PubMed

Saitoh, Yuu; Gotoh, Moritaka; Yoshizawa, Seiichiro; Akahane, Daigo; Fujimoto, Hiroaki; Ito, Yoshikazu; Ohyashiki, Kazuma

2018-01-01

A-46-year-old man was diagnosed with peripheral T cell lymphoma, not otherwise specified. He achieved a complete remission after pirarubicin, cyclophosphamide, vincristine, and prednisolone (THP-COP) therapy and successful autologous peripheral blood stem-cell transplantation (AutoSCT). However, 6 months post AutoSCT, he complained of fever. Chest computed tomography of the patient displayed bilateral interstitial pneumonitis. Human herpesvirus-6 (HHV-6) DNA was detected in his bronchoalveolar lavage fluid. Therefore, the patient was confirmed for HHV-6 pneumonitis. The treatment with foscarnet was effective, and no relapse was noticed in the patient. Besides, we have experienced pneumonitis of unknown origin in some patients after autologous or allogeneic stem-cell transplantations. Moreover, most of the above patients were clinically diagnosed using serum or plasma markers. Therefore, examining respiratory symptoms after AutoSCT would enable a more accurate diagnosis as well as treatment of patients with HHV-6 pneumonitis.

[The effect of isoflurane on the secretion of TNF-alpha and IL-1 beta from LPS-stimulated human peripheral blood monocytes].

PubMed

Sato, W; Enzan, K; Masaki, Y; Kayaba, M; Suzuki, M

1995-07-01

The cytokines such as tumor necrosis factor and interleukin-1 secreted from macrophages/monocytes proved to play important roles in the pathogenesis of endotoxemia, severe pancreatitis and other surgical injuries. However, it is still unclear how inhalational anesthetic agents influence the secretion of these cytokines from macrophages/monocytes. We investigated the effects of isoflurane on TNF-alpha and IL-1 beta secretions from human peripheral blood monocytes stimulated by lipopolysaccharide. TNF-alpha and IL-1 beta secretions increased after LPS stimulation and this increase was inhibited by isoflurane in dose-dependent fashion. The inhibitory action of isoflurane disappeared between 1 and 3 hours after stopping isoflurane inhalation. We concluded that isoflurane could inhibit TNF-alpha and IL-1 beta secretions from peripheral blood monocytes stimulated by LPS in a dose-dependent fashion and that the inhibitory action of isoflurane was reversible.

Capsaicin-evoked iCGRP release from human dental pulp: a model system for the study of peripheral neuropeptide secretion in normal healthy tissue

PubMed Central

Fehrenbacher, Jill C.; Sun, Xiaoling X.; Locke, Erin E.; Henry, Michael A.; Hargreaves, Kenneth M.

2009-01-01

The mechanisms underlying trigeminal pain conditions are incompletely understood. In vitro animal studies have elucidated various targets for pharmacological intervention; however, a lack of clinical models that allow evaluation of viable innervated human tissue has impeded successful translation of many preclinical findings into clinical therapeutics. Therefore, we developed and characterized an in vitro method that evaluates the responsiveness of isolated human nociceptors by measuring basal and stimulated release of neuropeptides from collected dental pulp biopsies. Informed consent was obtained from patients presenting for extraction of normal wisdom teeth. Patients were anesthetized using nerve block injection, teeth were extracted and bisected, and pulp was removed and superfused in vitro. Basal and capsaicin-evoked peripheral release of immunoreactive calcitonin gene-related peptide (iCGRP) was analyzed by enzyme immunoassay. The presence of nociceptive markers within neurons of the dental pulp was characterized using confocal microscopy. Capsaicin increased the release of iCGRP from dental pulp biopsies in a concentration-dependent manner. Stimulated release was dependent on extracellular calcium, reversed by a TRPV1 receptor antagonist, and desensitized acutely (tachyphylaxis) and pharmacologically by pretreatment with capsaicin. Superfusion with phorbol 12-myristate 13-acetate (PMA) increased basal and stimulated release, whereas PGE2 augmented only basal release. Compared with vehicle treatment, pretreatment with PGE2 induced competence for DAMGO to inhibit capsaicin-stimulated iCGRP release, similar to observations in animal models where inflammatory mediators induce competence for opioid inhibition. These results indicate the release of iCGRP from human dental pulp provides a novel tool to determine the effects of pharmacological compounds on human nociceptor sensitivity. PMID:19428185

Simple Radiowave-Based Method For Measuring Peripheral Blood Flow Project

NASA Technical Reports Server (NTRS)

Oliva-Buisson, Yvette J.

2014-01-01

Project objective is to design small radio frequency based flow probes for the measurement of blood flow velocity in peripheral arteries such as the femoral artery and middle cerebral artery. The result will be the technological capability to measure peripheral blood flow rates and flow changes during various environmental stressors such as microgravity without contact to the individual being monitored. This technology may also lead to an easier method of detecting venous gas emboli during extravehicular activities.

Learning outcomes and student-perceived value of clay modeling and cat dissection in undergraduate human anatomy and physiology.

PubMed

DeHoff, Mary Ellen; Clark, Krista L; Meganathan, Karthikeyan

2011-03-01

Alternatives and/or supplements to animal dissection are being explored by educators of human anatomy at different academic levels. Clay modeling is one such alternative that provides a kinesthetic, three-dimensional, constructive, and sensory approach to learning human anatomy. The present study compared two laboratory techniques, clay modeling of human anatomy and dissection of preserved cat specimens, in the instruction of muscles, peripheral nerves, and blood vessels. Specifically, we examined the effect of each technique on student performance on low-order and high-order questions related to each body system as well as the student-perceived value of each technique. Students who modeled anatomic structures in clay scored significantly higher on low-order questions related to peripheral nerves; scores were comparable between groups for high-order questions on peripheral nerves and for questions on muscles and blood vessels. Likert-scale surveys were used to measure student responses to statements about each laboratory technique. A significantly greater percentage of students in the clay modeling group "agreed" or "strongly agreed" with positive statements about their respective technique. These results indicate that clay modeling and cat dissection are equally effective in achieving student learning outcomes for certain systems in undergraduate human anatomy. Furthermore, clay modeling appears to be the preferred technique based on students' subjective perceptions of value to their learning experience.

CONTENT VALIDITY OF SYMPTOM-BASED MEASURES FOR DIABETIC, CHEMOTHERAPY, AND HIV PERIPHERAL NEUROPATHY

PubMed Central

GEWANDTER, JENNIFER S.; BURKE, LAURIE; CAVALETTI, GUIDO; DWORKIN, ROBERT H.; GIBBONS, CHRISTOPHER; GOVER, TONY D.; HERRMANN, DAVID N.; MCARTHUR, JUSTIN C.; MCDERMOTT, MICHAEL P.; RAPPAPORT, BOB A.; REEVE, BRYCE B.; RUSSELL, JAMES W.; SMITH, A. GORDON; SMITH, SHANNON M.; TURK, DENNIS C.; VINIK, AARON I.; FREEMAN, ROY

2017-01-01

Introduction No treatments for axonal peripheral neuropathy are approved by the United States Food and Drug Administration (FDA). Although patient- and clinician-reported outcomes are central to evaluating neuropathy symptoms, they can be difficult to assess accurately. The inability to identify efficacious treatments for peripheral neuropathies could be due to invalid or inadequate outcome measures. Methods This systematic review examined the content validity of symptom-based measures of diabetic peripheral neuropathy, HIV neuropathy, and chemotherapy-induced peripheral neuropathy. Results Use of all FDA-recommended methods to establish content validity was only reported for 2 of 18 measures. Multiple sensory and motor symptoms were included in measures for all 3 conditions; these included numbness, tingling, pain, allodynia, difficulty walking, and cramping. Autonomic symptoms were less frequently included. Conclusions Given significant overlap in symptoms between neuropathy etiologies, a measure with content validity for multiple neuropathies with supplemental disease-specific modules could be of great value in the development of disease-modifying treatments for peripheral neuropathies. PMID:27447116

Alteration of peripheral blood monocyte gene expression in humans following diesel exhaust inhalation

PubMed Central

Pettit, Ashley P.; Brooks, Andrew; Laumbach, Robert; Fiedler, Nancy; Wang, Qi; Strickland, Pamela Ohman; Madura, Kiran; Zhang, Junfeng; Kipen, Howard M.

2013-01-01

Context Epidemiologic associations between acutely increased cardiorespiratory morbidity and mortality and particulate air pollution are well established, but the effects of acute pollution exposure on human gene expression changes are not well understood. Objective In order to identify potential mechanisms underlying epidemiologic associations between air pollution and morbidity, we explored changes in gene expression in humans following inhalation of fresh diesel exhaust (DE), a model for particulate air pollution. Materials and methods Fourteen ethnically homogeneous (white males), young, healthy subjects underwent 60-min inhalation exposures on 2 separate days with clean filtered air (CA) or freshly generated and diluted DE at a concentration of 300 μg/m3 PM2.5. Prior to and 24 h following each session, whole blood was sampled and fractionated for peripheral blood mononuclear cell (PBMC) isolation, RNA extraction, and generation of cDNA, followed by hybridization with Agilent Whole Human Genome (4X44K) arrays. Results Oxidative stress and the ubiquitin proteasome pathway, as well as the coagulation system, were among hypothesized pathways identified by analysis of differentially expressed genes. Nine genes from these pathways were validated using real-time polymerase chain reaction (PCR) to compare fold change in expression between DE exposed and CA days. Quantitative gene fold changes generated by real-time PCR were directionally consistent with the fold changes from the microarray analysis. Discussion and conclusion Changes in gene expression connected with key oxidative stress, protein degradation, and coagulation pathways are likely to underlie observed physiologic and clinical outcomes and suggest specific avenues and sensitive time points for further physiologic exploration. PMID:22369193

Peripheral Nerve Regeneration by Secretomes of Stem Cells from Human Exfoliated Deciduous Teeth.

PubMed

Sugimura-Wakayama, Yukiko; Katagiri, Wataru; Osugi, Masashi; Kawai, Takamasa; Ogata, Kenichi; Sakaguchi, Kohei; Hibi, Hideharu

2015-11-15

Peripheral nerve regeneration across nerve gaps is often suboptimal, with poor functional recovery. Stem cell transplantation-based regenerative therapy is a promising approach for axon regeneration and functional recovery of peripheral nerve injury; however, the mechanisms remain controversial and unclear. Recent studies suggest that transplanted stem cells promote tissue regeneration through a paracrine mechanism. We investigated the effects of conditioned media derived from stem cells from human exfoliated deciduous teeth (SHED-CM) on peripheral nerve regeneration. In vitro, SHED-CM-treated Schwann cells exhibited significantly increased proliferation, migration, and the expression of neuron-, extracellular matrix (ECM)-, and angiogenesis-related genes. SHED-CM stimulated neuritogenesis of dorsal root ganglia and increased cell viability. Similarly, SHED-CM enhanced tube formation in an angiogenesis assay. In vivo, a 10-mm rat sciatic nerve gap model was bridged by silicon conduits containing SHED-CM or serum-free Dulbecco's modified Eagle's medium. Light and electron microscopy confirmed that the number of myelinated axons and axon-to-fiber ratio (G-ratio) were significantly higher in the SHED-CM group at 12 weeks after nerve transection surgery. The sciatic functional index (SFI) and gastrocnemius (target muscle) wet weight ratio demonstrated functional recovery. Increased compound muscle action potentials and increased SFI in the SHED-CM group suggested sciatic nerve reinnervation of the target muscle and improved functional recovery. We also observed reduced muscle atrophy in the SHED-CM group. Thus, SHEDs may secrete various trophic factors that enhance peripheral nerve regeneration through multiple mechanisms. SHED-CM may therefore provide a novel therapy that creates a more desirable extracellular microenvironment for peripheral nerve regeneration.

Peripheral metabolic actions of leptin.

PubMed

Muoio, Deborah M; Lynis Dohm, G

2002-12-01

The adipocyte-derived hormone, leptin, regulates food intake and systemic fuel metabolism; ob /ob mice, which lack functional leptin, exhibit an obesity syndrome that is similar to morbid obesity in humans. Leptin receptors are expressed most abundantly in the brain but are also present in several peripheral tissues. The role of leptin in controlling energy homeostasis has thus far focused on brain receptors and neuroendocrine pathways that regulate feeding behaviour and sympathetic nervous system activity. This chapter focuses on mounting evidence that leptin's effects on energy balance are also mediated by direct peripheral actions on key metabolic organs such as skeletal muscle, liver, pancreas and adipose tissue. Strong evidence indicates that peripheral leptin receptors regulate cellular lipid balance, favouring beta-oxidation over triacylglycerol storage. There are data to indicate that peripheral leptin also modulates glucose metabolism and insulin action; however, its precise role in controlling gluco-regulatory pathways remains uncertain and requires further investigation.

Stem cell and peripheral nerve injury and repair.

PubMed

Dong, Ming-min; Yi, Tian-hua

2010-10-01

Peripheral motor nerve injuries are a significant source of morbidity. Neural stem cells (NSCs), a group of relatively primitive cells, possess self-renewal ability and multidifferentiation potential. NSCs may be successfully separated from the human embryo and central nervous system (CNS) and differentiated into mature neurons and gliacytes by in vitro induction or transplantation into the body and may be differentiated into Schwann-like cells under specific conditions. It has been demonstrated that the ability of peripheral nerves to regenerate is mainly attributable to Schwann cells. NSC transplantation can promote peripheral nerve regeneration and provide a new means for treatment of peripheral nerve injury. In recent years, the study of NSCs has become a focus of many laboratories, but the biological characteristics and differentiation regulation mechanisms are not fully clear. In this article, we provide a brief review of NSC characteristics, cultivation, oriented differentiation, and clinical application. © Thieme Medical Publishers.

Peripheral refraction and image blur in four meridians in emmetropes and myopes.

PubMed

Shen, Jie; Spors, Frank; Egan, Donald; Liu, Chunming

2018-01-01

The peripheral refractive error of the human eye has been hypothesized to be a major stimulus for the development of its central refractive error. The purpose of this study was to investigate the changes in the peripheral refractive error across horizontal, vertical and two diagonal meridians in emmetropic and low, moderate and high myopic adults. Thirty-four adult subjects were recruited and aberration was measured using a modified commercial aberrometer. We then computed the refractive error in power vector notation from second-order Zernike terms. Statistical analysis was performed to evaluate the statistical differences in refractive error profiles between the subject groups and across all measured visual field meridians. Small amounts of relative myopic shift were observed in emmetropic and low myopic subjects. However, moderate and high myopic subjects exhibited a relative hyperopic shift in all four meridians. Astigmatism J 0 and J 45 had quadratic or linear changes dependent on the visual field meridians. Peripheral Sphero-Cylindrical Retinal Image Blur increased in emmetropic eyes in most of the measured visual fields. The findings indicate an overall emmetropic or slightly relative myopic periphery (spherical or oblate retinal shape) formed in emmetropes and low myopes, while moderate and high myopes form relative hyperopic periphery (prolate, or less oblate, retinal shape). In general, human emmetropic eyes demonstrate higher amount of peripheral retinal image blur.

INDUCTION OF DNA STRAND BREAKS BY TRIHALOMETHANES IN PRIMARY HUMAN LUNG EPITHELIAL CELLS

EPA Science Inventory

Abstract

Trihalomethanes (TEMs) are disinfection by-products and suspected human carcinogens present in chlorinated drinking water. Previous studies have shown that many THMs induce sister chromatid exchanges and DNA strand breaks in human peripheral blood lymphocyte...

Lumped parametric model of the human ear for sound transmission.

PubMed

Feng, Bin; Gan, Rong Z

2004-09-01

A lumped parametric model of the human auditoria peripherals consisting of six masses suspended with six springs and ten dashpots was proposed. This model will provide the quantitative basis for the construction of a physical model of the human middle ear. The lumped model parameters were first identified using published anatomical data, and then determined through a parameter optimization process. The transfer function of the middle ear obtained from human temporal bone experiments with laser Doppler interferometers was used for creating the target function during the optimization process. It was found that, among 14 spring and dashpot parameters, there were five parameters which had pronounced effects on the dynamic behaviors of the model. The detailed discussion on the sensitivity of those parameters was provided with appropriate applications for sound transmission in the ear. We expect that the methods for characterizing the lumped model of the human ear and the model parameters will be useful for theoretical modeling of the ear function and construction of the ear physical model.

A sensitive ELISA for measuring the adhesion of leukocytic cells to human endothelial cells.

PubMed

Krakauer, T

1994-12-28

A new, sensitive ELISA using monoclonal antibodies reactive with surface molecules specific for various leukocytes was devised to measure the attachment of these cells to cultured monolayers of human umbilical vein endothelial cells. Preparations of peripheral blood mononuclear cells, a human monocytic cell line (THP-1) and a human lymphoblastic T cell line (MOLT-4) were used to test the sensitivity of this method and compare it with the conventional 51Cr-radiolabeled cell assay. The extent of adhesion to endothelial cells was assayed by measuring the optical density produced by a complex of peroxidase-labeled streptavidin, biotin-conjugated F(ab')2 anti-mouse Ig and monoclonal antibody on fixed leukocytic cells that had adhered to endothelial cells. This method is fast and sensitive, eliminates the use of radioisotopes, and, because the detection uses a specific marker on the cell of interest, can be used in preparations of unseparated mixtures of cells. As this is a microassay, using relatively small number of cells and reagents, the methodology can be applied to screen a large number of therapeutic agents that may regulate adhesion. Using this method, the anti-inflammatory corticosteroid, dexamethasone, was found to inhibit the adhesion of THP-1 and MOLT-4 cells to cytokine-activated endothelial cells.

Effect of limb cooling on peripheral and global oxygen consumption in neonates

PubMed Central

Hassan, I; Wickramasinghe, Y; Spencer, S

2003-01-01

Aim: To evaluate peripheral oxygen consumption (VO2) measurements using near infrared spectroscopy (NIRS) with arterial occlusion in healthy term neonates by studying the effect of limb cooling on peripheral and global VO2. Subjects and methods: Twenty two healthy term neonates were studied. Peripheral VO2 was measured by NIRS using arterial occlusion and measurement of the oxyhaemoglobin (HbO2) decrement slope. Global VO2 was measured by open circuit calorimetry. Global and peripheral VO2 was measured in each neonate before and after limb cooling. Results: In 10 neonates, a fall in forearm temperature of 2.2°C (mild cooling) decreased forearm VO2 by 19.6% (p < 0.01). Global VO2 did not change. In 12 neonates, a fall in forearm temperature of 4°C (moderate cooling) decreased forearm VO2 by 34.7% (p < 0.01). Global VO2 increased by 17.6% (p < 0.05). Conclusions: The NIRS arterial occlusion method is able to measure changes in peripheral VO2 induced by limb cooling. The changes are more pronounced with moderate limb cooling when a concomitant rise in global VO2 is observed. Change in peripheral temperature must be taken into consideration in the interpretation of peripheral VO2 measurements in neonates. PMID:12598504

Determination of plasma volume by indocyanine green--validation of the method and use in patients after cardiopulmonary bypass.

PubMed

Menth-Meier, S E; Imoberdorf, R; Regli, B; Kipfer, B; Turgay, M; Ballmer, P E

2001-05-01

Validation of plasma volume (PV) determination by indocyanine green (ICG) in comparison to the gold-standard method with radioiodinated albumin, and investigation of the effect of commonly used plasma expanders (albumin, hydroxyethyl starch, and polygelatine) on PV in the early postoperative phase in patients undergoing cardiac surgery. Prospective clinical study. Department of medicine and intensive care unit at a university hospital. Ten healthy volunteers and 21 patients after elective open-heart surgery. PV of subjects was measured by i.v. injecting 5 microCi [125I]albumin (I-ALB). One hour later, PV was determined by a peripheral i. v. injection of 0.25 mg/kg body weight ICG (ICG1). In five subjects PV was measured repeatedly by ICG (ICG2) 1 h after ICG1. Mean PV of I-ALB and ICG1 or ICG2 showed consistent results. Further, we investigated central vs peripheral intravenous injection of ICG in six patients after open-heart surgery compared to [125I]albumin. There was no difference between mean PV measured by [125I]albumin and peripheral ICG (P = 0.40). PV determined by central injection of ICG was significantly higher than by the other methods. In 15 patients PV was determined by [125I]albumin. Thereafter, patients were randomly divided into three groups. Group ALB was infused with 1.75 ml/kg body weight human albumin 20%, group HAES with 5.25 ml/kg body weight hydroxyethyl starch 6%, and group HAEM with 7.0 ml/kg body weight polygelatine 3.5%. PV was measured 1 h and 4 h after infusion by ICG. There were no significant changes in PV between the groups. PV determination by peripheral i. v. injection of ICG produced reliable and consistent results when a reactive hyperaemia was produced by a tourniquet prior to injection. Therefore, central venous injection of ICG may not be prerequisite for precise measurements of PV. The expected acute increase in PV after infusion of commonly used plasma expanders after cardiac surgery was not found.

Rapid CD4(+) T-cell loss induced by human immunodeficiency virus type 1(NC) in uninfected and previously infected chimpanzees.

PubMed

Novembre, F J; de Rosayro, J; Nidtha, S; O'Neil, S P; Gibson, T R; Evans-Strickfaden, T; Hart, C E; McClure, H M

2001-02-01

To investigate the pathogenicity of a virus originating in a chimpanzee with AIDS (C499), two chimpanzees were inoculated with a plasma-derived isolate termed human immunodeficiency virus type 1(NC) (HIV-1(NC)). A previously uninfected chimpanzee, C534, experienced rapid peripheral CD4(+) T-cell loss to fewer than 26 cells/microl by 14 weeks after infection. CD4(+) T-cell depletion was associated with high plasma HIV-1 loads but a low virus burden in the peripheral lymph node. The second chimpanzee, C459, infected 13 years previously with HIV-1(LAV), experienced a more protracted course of peripheral CD4(+) T-cell loss after HIV-1(NC) inoculation, resulting in fewer than 200 cells/microl by 96 weeks postinoculation. The quantities of viral RNA in the plasma and peripheral lymph node from C459 were below the lower limits of detection prior to inoculation with HIV-1(NC) but were significantly and persistently increased after superinfection, with HIV-1(NC) representing the predominant viral genotype. These results show that viruses derived from C499 are more pathogenic for chimpanzees than any other HIV-1 isolates described to date.

Bancroftian filariasis in Maceio, state of Alagoas, Brazil: Observations on Culex quinquefasciatus after blood feeding on individuals with different densities of microfilariae in the peripheral blood stream.

PubMed

Brito, A C; Fontes, G; Williams, P; Rocha, E M

1998-04-01

Females of laboratory-reared Culex quinquefasciatus were allowed to take blood meals on individuals with low (1-100 microfilariae/ml of peripheral blood), moderate (101-500 microfilariae/ml), and high (> 500 microfilariae/ml) microfilaremia. The mosquitoes ingested 1.39-3.80 microl of blood and infective third-stage (L3) larvae were first recorded 13-14 days after the infecting blood meal. The number of microfilariae ingested by mosquitoes was proportional to the density of microfilariae in the peripheral blood of the human subjects, but with a concentration factor of up to 6.5 times the expected number. Survival of mosquitoes was not influenced by the density of microfilariae in the peripheral blood of infected individuals. Infectivity indices were proportional to microfilaremia in human subjects. The number of L3 larvae/female (intensity of infection) was not influenced by individual microfilaremia. The highest vector efficiency and the best experimental infection index were recorded in mosquitoes that blood fed on individuals with moderate microfilaremia. The results are discussed in relation to the transmission on Bancroftian filariasis in the study area.

Strategies to promote peripheral nerve regeneration: electrical stimulation and/or exercise

PubMed Central

Gordon, Tessa; English, Arthur W.

2015-01-01

Enhancing the regeneration of axons is often considered a therapeutic target for improving functional recovery after peripheral nerve injury. In this review, the evidence for the efficacy of electrical stimulation (ES), daily exercise, and their combination in promoting nerve regeneration after peripheral nerve injuries in both animal models and in human patients, is explored. The rationale, effectiveness, and molecular basis of ES and exercise in accelerating axon outgrowth are reviewed. In comparing the effects of ES and exercise in enhancing axon regeneration, increased neural activity, neurotrophins, and androgens are considered common requirements. Similar, gender-specific requirements are found for exercise to enhance axon regeneration in the periphery and for sustaining synaptic inputs onto injured motoneurons. ES promotes nerve regeneration after delayed nerve repair in humans and rats. The effectiveness of exercise is less clear. Although ES, but not exercise, results in a significant misdirection of regenerating motor axons to reinnervate different muscle targets, the loss of neuromuscular specificity encountered has only a very small impact on resulting functional recovery. Both ES and exercise are promising experimental treatments for peripheral nerve injury that seem ready to be translated to clinical use. PMID:26121368

Lymphocyte sensitization to nervous tissues and muscle in patients with the Guillain-Barré syndrome

PubMed Central

Caspary, E. A.; Currie, S.; Walton, J. N.; Field, E. J.

1971-01-01

By means of an electrophoretic method lymphocytes from patients with the Guillain-Barré syndrome (`acute idiopathic polyneuritis') have been shown to be sensitized to both encephalitogenic factor (EF) and a similar basic protein prepared from human sciatic nerve (SNBP). Sensitization was more marked in the acute stage of the disorder during which there also appeared to be a degree of sensitization to muscle. The results are consistent with the view that lymphocytic infiltration of peripheral nerves in the condition is of pathogenetic significance. PMID:5106345

The variable presentations and broadening geographic distribution of hepatic fascioliasis.

PubMed

Rowan, Sarah E; Levi, Marilyn E; Youngwerth, Jean M; Brauer, Brian; Everson, Gregory T; Johnson, Steven C

2012-06-01

We report 2 unrelated cases of hepatic fascioliasis in travelers returning to the United States from Africa and the Middle East. The first case presented with acute infection. Prominent clinical features included abdominal pain, elevated liver transaminases, serpiginous hepatic lesions, pericapsular hematoma, and marked peripheral eosinophilia. The second case was diagnosed in the chronic stage of infection and presented with right upper quadrant abdominal pain, cystic hepatic lesions, and an adult fluke in the common bile duct. We review the life cycle of Fasciola species, the corresponding clinical features during the stages of human infection, diagnostic methods, and the evolving understanding of the epidemiology of human fascioliasis, particularly emphasizing fascioliasis in African countries. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

T cell activity in successful treatment of chronic urticaria with omalizumab

PubMed Central

2011-01-01

Omalizumab, a humanized monoclonal anti-IgE antibody has the potential to alter allergen processing. Recently, it has been postulated the assessment of PHA-stimulated adenosine triphosphate (ATP) activity as maker of CD4+ T cells activity in peripheral blood cells. We present the case report of a 35-year-old woman with a history of chronic idiopathic urticaria and angioedema of 8 years of development with poor response to treatment. The patient was partially controlled with cyclosporine at doses of 100 mg/12 h. However, she was still developing hives daily. Finally treatment with omalizumab was started at dose of 300 mg every 2 weeks. The patient experienced a decrease in urticarial lesions 2 days after starting therapy. We also evaluated the effects of omalizumab therapy on the activity of peripheral blood CD4+ T cells from the patient, in order to determine the potential modification of anti-IgE therapy on the process of antigen presentation-recognition. Activity of CD4+ cells by ATP release was clearly increased demonstrating an enlarged CD4 activity. Omalizumab may be useful in the treatment of severe chronic urticaria. ATP activity of peripheral blood CD4+ T cells might be a non-subjective method to assess Omalizumab activity. PMID:21791043

Human multidrug resistance protein 8 (MRP8/ABCC11), an apical efflux pump for steroid sulfates, is an axonal protein of the CNS and peripheral nervous system.

PubMed

Bortfeld, M; Rius, M; König, J; Herold-Mende, C; Nies, A T; Keppler, D

2006-01-01

Dehydroepiandrosterone 3-sulfate and other neurosteroids are synthesized in the CNS and peripheral nervous system where they may modulate neuronal excitability by interacting with ligand-gated ion channels. For this modulatory activity, neurosteroids have to be locally released from either neurons or glial cells. We here identify the integral membrane protein ABCC11 (multidrug resistance protein 8) as an ATP-dependent efflux pump for steroid sulfates, including dehydroepiandrosterone 3-sulfate, and localize it to axons of the human CNS and peripheral nervous system. ABCC11 mRNA was detected in human brain by real-time polymerase chain reaction. Antibodies raised against ABCC11 served to detect the protein in brain by immunoblotting and immunofluorescence microscopy. ABCC11 was preferentially found in the white matter of the brain and co-localized with neurofilaments indicating that it is an axonal protein. Additionally, ABCC11 was localized to axons of the peripheral nervous system. For functional studies, ABCC11 was expressed in polarized Madin-Darby canine kidney cells where it was sorted to the apical membrane. This apical sorting is in accordance with the localization of ABCC11 to the axonal membrane of neurons. Inside-out plasma membrane vesicles containing recombinant ABCC11 mediated ATP-dependent transport of dehydroepiandrosterone 3-sulfate with a Km value of 21 microM. This transport function together with the localization of the ABCC11 protein in vicinity to GABAA receptors is consistent with a role of ABCC11 in dehydroepiandrosterone 3-sulfate release from neurons to sites of dehydroepiandrosterone 3-sulfate-mediated receptor modulation. Our findings may provide a basis for the characterization of mutations in the human ABCC11 gene and their linkage with neurological disorders.

Peripheral biomarkers revisited: integrative profiling of peripheral samples for psychiatric research.

PubMed

Hayashi-Takagi, Akiko; Vawter, Marquis P; Iwamoto, Kazuya

2014-06-15

Peripheral samples, such as blood and skin, have been used for decades in psychiatric research as surrogates for central nervous system samples. Although the validity of the data obtained from peripheral samples has been questioned and other state-of-the-art techniques, such as human brain imaging, genomics, and induced pluripotent stem cells, seem to reduce the value of peripheral cells, accumulating evidence has suggested that revisiting peripheral samples is worthwhile. Here, we re-evaluate the utility of peripheral samples and argue that establishing an understanding of the common signaling and biological processes in the brain and peripheral samples is required for the validity of such models. First, we present an overview of the available types of peripheral cells and describe their advantages and disadvantages. We then briefly summarize the main achievements of omics studies, including epigenome, transcriptome, proteome, and metabolome analyses, as well as the main findings of functional cellular assays, the results of which imply that alterations in neurotransmission, metabolism, the cell cycle, and the immune system may be partially responsible for the pathophysiology of major psychiatric disorders such as schizophrenia. Finally, we discuss the future utility of peripheral samples for the development of biomarkers and tailor-made therapies, such as multimodal assays that are used as a battery of disease and trait pathways and that might be potent and complimentary tools for use in psychiatric research. © 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.

PERIPHERAL PARASITAEMIA AND ITS ASSOCIATION WITH PLASMA CYTOKINES LEVELS IN MALARIA-INFECTED PREGNANT WOMEN IN ABA, ABIA STATE, NIGERIA

PubMed Central

Ifeanyichukwu, M.O.; Okamgba, O.C.; Amilo, G.I.; Nwokorie, E.A.

2017-01-01

Background: Cytokines in pregnant female may not be a normal phenomenon as malarial infection is often associated with strong CD4+ cell activation and up-regulation of pro-inflammatory cytokines. We investigated the relationship between peripheral parasitaemia and plasma levels of cytokines among malaria infected pregnant women in Aba, Abia State, Nigeria. Materials and Methods: A total of 206 non-HIV positive asymptomatic malaria parasitaemic (n=144) and non-parasitaemic (n=62) pregnant women were recruited for this study alongside 80 non-pregnant women who served as positive (n=40) and negative (n=40) controls. Blood samples were aseptically collected from each subject and tested for HIV and malaria parasites using standard methods. Also, plasma levels of cytokines were measured using Th1/Th2 human cytokine ELISA kits (Abcam, UK). Analysis of Variance and Student’s t-test were used for Comparison of groups while Pearson’s Correlation Coefficient was used for tests of association. Results: The results revealed a mean parasite density of 685.56±484.55 parasites/µl of blood. Malaria infected pregnant subjects showed significantly higher levels of IFN-γ, TNF-α, IL-4, IL-6 and IL-10 when compared with their non-infected counterparts (P< 0.05). The cytokines evaluated were higher in moderate parasitaemia than mild parasitaemia. Positive correlation existed between peripheral parasite density (PPD) and IL-4 (r= 0.24, P=0.004), PPD and IL-6 (r = 0.35, P = 0.001) as well as PPD and IL-10 (r = 0.29, P = 0.001). Conclusion: This study showed that increase in peripheral parasitaemia increased levels of some plasma cytokines (IL-4, IL-6 and IL-10) but not IFN-γ and TNF-α in the malaria infected pregnant women studied. PMID:28670640

A STUDY OF THE SPINAL CORD BY NISSL'S METHOD IN TYPHOID FEVER AND IN EXPERIMENTAL INFECTION WITH THE TYPHOID BACILLUS.

PubMed

Nichols, J L

1899-03-01

(1) The application of the Nissl method to the study of the motor cells of the spinal cord, and the nerve cells of the dorsal root ganglia in typhoid fever, shows that these cells regularly suffer pathological changes in the course of the infection. (2) The alterations in the motor cells are more constant and of a severer grade than are those in the cells of the sensory ganglia. The more characteristic changes consist of disintegration, solution and destruction of the chromatic substance of the cell starting from the axone hillock and proceeding toward the nucleus. Coincidently the nuclei of the affected cells seek the periphery. Alterations are also suffered by the nucleus and nucleolus. (3) While this central form of ehromatolysis is the prevailing type of pathological change, disintegration, etc., of the Nissl bodies situated in the periphery of the cell and in the dendrites is also observed (peripheral chromatolysis). (4) In experimental infection with typhoid bacilli in rabbits a similar series of lesions in the corresponding nerve cells in the spinal cord and ganglia is encountered. (5) The main or central type of lesions discovered is identical with that found in man and animals after section, destruction, or even slight injury of the peripheral nerves. (6) The examination of the peripheral nerves arising from the lumbar segment of the cord (the site in man and rabbit of the most profound changes) in rabbits inoculated with typhoid bacilli showed well-marked evidences of parenchymatous degeneration. (7> It is probable that lesions of the peripheral nerves in typhoid fever in human beings are common and that the post-typhoid hyper sthesias and paralyses are due to this cause. (8) Restitution of the chromatic granules may take place in the affected nerve cells, the new formation beginning about the nucleus and extending through the protoplasm.

A STUDY OF THE SPINAL CORD BY NISSL'S METHOD IN TYPHOID FEVER AND IN EXPERIMENTAL INFECTION WITH THE TYPHOID BACILLUS

PubMed Central

Nichols, Joseph Longworth

1899-01-01

(1) The application of the Nissl method to the study of the motor cells of the spinal cord, and the nerve cells of the dorsal root ganglia in typhoid fever, shows that these cells regularly suffer pathological changes in the course of the infection. (2) The alterations in the motor cells are more constant and of a severer grade than are those in the cells of the sensory ganglia. The more characteristic changes consist of disintegration, solution and destruction of the chromatic substance of the cell starting from the axone hillock and proceeding toward the nucleus. Coincidently the nuclei of the affected cells seek the periphery. Alterations are also suffered by the nucleus and nucleolus. (3) While this central form of ehromatolysis is the prevailing type of pathological change, disintegration, etc., of the Nissl bodies situated in the periphery of the cell and in the dendrites is also observed (peripheral chromatolysis). (4) In experimental infection with typhoid bacilli in rabbits a similar series of lesions in the corresponding nerve cells in the spinal cord and ganglia is encountered. (5) The main or central type of lesions discovered is identical with that found in man and animals after section, destruction, or even slight injury of the peripheral nerves. (6) The examination of the peripheral nerves arising from the lumbar segment of the cord (the site in man and rabbit of the most profound changes) in rabbits inoculated with typhoid bacilli showed well-marked evidences of parenchymatous degeneration. (7> It is probable that lesions of the peripheral nerves in typhoid fever in human beings are common and that the post-typhoid hyper sthesias and paralyses are due to this cause. (8) Restitution of the chromatic granules may take place in the affected nerve cells, the new formation beginning about the nucleus and extending through the protoplasm. PMID:19866906

Methionine enkephalin (MENK) improves lymphocyte subpopulations in human peripheral blood of 50 cancer patients by inhibiting regulatory T cells (Tregs)

PubMed Central

Wang, Qiushi; Gao, Xinghua; Yuan, Zhe; Wang, Zhe; Meng, Yiming; Cao, Yan; Plotnikoff, Nicolas P; Griffin, Noreen; Shan, Fengping

2014-01-01

MENK, a penta-peptide is considered as being involved in the regulatory feedback loop between the immune and neuroendocrine systems, with marked modulation of various functions of human immune cells. The aim of the present work was to investigate change of lymphocyte subpopulations in peripheral blood of 50 cancer patients before and after treatment with MENK. Peripheral blood mononuclear cells (PBMCs) of peripheral blood from 50 cancer patients were isolated by density gradient centrifugation using Ficoll-Paque solution and cultured with MENK. We measured proliferation of total nucleated cells, subpopulations of individual CD4+T cells, CD8+T cells, CD4+CD25+ regulatory T cells (Treg), natural killer cells (NK) before and after treatment with 10-12M MENK in cell culture by flow cytometry (FCM). Our results indicated that MENK showed a strong inhibiting effect on Treg cells while it stimulated marked proliferation of other lymphocyte subpopulations. All data obtained were of significance statistically. It was therefore concluded that MENK could work as a strong immune booster with great potential in restoring damaged human immune system and we could consider MENK as a drug to treat cancer patients, whose immune systems are damaged by chemotherapy or radiotherapy. Furthermore we could consider MENK as a chemotherapy additive, which would sustain immune system of cancer patients during the process of chemotherapy to get maximized efficacy with minimized side effect. PMID:25424790

Analysis of cytotoxic effects of silver nanoclusters on human peripheral blood mononuclear cells 'in vitro'.

PubMed

Orta-García, Sandra Teresa; Plascencia-Villa, Germán; Ochoa-Martínez, Angeles Catalina; Ruiz-Vera, Tania; Pérez-Vázquez, Francisco Javier; Velázquez-Salazar, J Jesús; Yacamán, Miguel José; Navarro-Contreras, Hugo Ricardo; Pérez-Maldonado, Iván N

2015-10-01

The antimicrobial properties of silver nanoparticles (AgNPs) have made these particles one of the most used nanomaterials in consumer products. Therefore, an understanding of the interactions (unwanted toxicity) between nanoparticles and human cells is of significant interest. The aim of this study was to assess the in vitro cytotoxicity effects of silver nanoclusters (AgNC, < 2 nm diameter) on peripheral blood mononuclear cells (PBMC). Using flow cytometry and comet assay methods, we demonstrate that exposure of PBMC to AgNC induced intracellular reactive oxygen species (ROS) generation, DNA damage and apoptosis at 3, 6 and 12 h, with a dose-dependent response (0.1, 1, 3, 5 and 30 µg ml(-1)). Advanced electron microscopy imaging of complete and ultrathin-sections of PBMC confirmed the cytotoxic effects and cell damage caused by AgNC. The present study showed that AgNC produced without coating agents induced significant cytotoxic effects on PBMC owing to their high aspect ratio and active surface area, even at much lower concentrations (<1 µg ml(-1)) than those applied in previous studies, resembling what would occur under real exposure conditions to nanosilver-functionalized consumer products. Copyright © 2015 John Wiley & Sons, Ltd.

Sleep Loss as a Factor to Induce Cellular and Molecular Inflammatory Variations

PubMed Central

Hurtado-Alvarado, Gabriela; Castillo-García, Stephanie Ariadne; Hernández, María Eugenia; Domínguez-Salazar, Emilio; Velázquez-Moctezuma, Javier; Gómez-González, Beatriz

2013-01-01

A reduction in the amount of time spent sleeping occurs chronically in modern society. Clinical and experimental studies in humans and animal models have shown that immune function is impaired when sleep loss is experienced. Sleep loss exerts a strong regulatory influence on peripheral levels of inflammatory mediators of the immune response. An increasing number of research projects support the existence of reciprocal regulation between sleep and low-intensity inflammatory response. Recent studies show that sleep deficient humans and rodents exhibit a proinflammatory component; therefore, sleep loss is considered as a risk factor for developing cardiovascular, metabolic, and neurodegenerative diseases (e.g., diabetes, Alzheimer's disease, and multiple sclerosis). Circulating levels of proinflammatory mediators depend on the intensity and duration of the method employed to induce sleep loss. Recognizing the fact that the concentration of proinflammatory mediators is different between acute and chronic sleep-loss may expand the understanding of the relationship between sleep and the immune response. The aim of this review is to integrate data from recent published reports (2002–2013) on the effects of sleep loss on the immune response. This review may allow readers to have an integrated view of the mechanisms involved in central and peripheral deficits induced by sleep loss. PMID:24367384

Serum amyloid A secretion from monocytic leukaemia cell line THP-1 and cultured human peripheral monocytes.

PubMed

Yamada, T; Wada, A; Itoh, K; Igari, J

2000-07-01

Serum amyloid A (SAA), an acute-phase protein and a precursor of fibrous components in reactive amyloid deposits, is synthesized mainly in the liver under the stimulation of inflammation-related cytokines. In addition, the SAA gene is expressed in monocytes/macrophages, which are believed to play a central role in amyloid fibrillogenesis. Consequently, the pathogenic implication of SAA produced from these cells has been of major concern. Because SAA synthesis at the protein level in such cells has never been analyzed quantitatively, in this study an enzyme-linked immunosorbent assay was generated with a detection level sufficiently high to measure SAA concentrations in the culture supernatants of the human monocytic leukaemia cell line THP-1. SAA secretion by THP-1 with interleukin (IL)-1beta required the presence of dexamethasone as proposed previously. We also found that unidentified components in fetal calf serum (FCS) could induce SAA production by THP-1 in the presence of dexamethasone. These findings are in contrast to the results obtained from hepatoma cell line HepG2, in which IL-1beta alone could induce SAA secretion, while dexamethasone-supplemented FCS could not. The method was able to quantify SAA secreted from cultured human peripheral monocytes. The findings suggest that monocytes produce SAA in almost the same manner as THP-1. Thus, THP-1 cells can be utilized to investigate a distinctive manner of SAA production from monocytes.

Macrophage Depletion Ameliorates Peripheral Neuropathy in Aging Mice.

PubMed

Yuan, Xidi; Klein, Dennis; Kerscher, Susanne; West, Brian L; Weis, Joachim; Katona, Istvan; Martini, Rudolf

2018-05-09

Aging is known as a major risk factor for the structure and function of the nervous system. There is urgent need to overcome such deleterious effects of age-related neurodegeneration. Here we show that peripheral nerves of 24-month-old aging C57BL/6 mice of either sex show similar pathological alterations as nerves from aging human individuals, whereas 12-month-old adult mice lack such alterations. Specifically, nerve fibers showed demyelination, remyelination and axonal lesion. Moreover, in the aging mice, neuromuscular junctions showed features typical for dying-back neuropathies, as revealed by a decline of presynaptic markers, associated with α-bungarotoxin-positive postsynapses. In line with these observations were reduced muscle strengths. These alterations were accompanied by elevated numbers of endoneurial macrophages, partially comprising the features of phagocytosing macrophages. Comparable profiles of macrophages could be identified in peripheral nerve biopsies of aging persons. To determine the pathological impact of macrophages in aging mice, we selectively targeted the cells by applying an orally administered CSF-1R specific kinase (c-FMS) inhibitor. The 6-month-lasting treatment started before development of degenerative changes at 18 months and reduced macrophage numbers in mice by ∼70%, without side effects. Strikingly, nerve structure was ameliorated and muscle strength preserved. We show, for the first time, that age-related degenerative changes in peripheral nerves are driven by macrophages. These findings may pave the way for treating degeneration in the aging peripheral nervous system by targeting macrophages, leading to reduced weakness, improved mobility, and eventually increased quality of life in the elderly. SIGNIFICANCE STATEMENT Aging is a major risk factor for the structure and function of the nervous system. Here we show that peripheral nerves of 24-month-old aging mice show similar degenerative alterations as nerves from aging human individuals. Both in mice and humans, these alterations were accompanied by endoneurial macrophages. To determine the pathological impact of macrophages in aging mice, we selectively targeted the cells by blocking a cytokine receptor, essential for macrophage survival. The treatment strongly reduced macrophage numbers and substantially improved nerve structure and muscle strength. We show, for the first time, that age-related degenerative changes in peripheral nerves are driven by macrophages. These findings may be helpful for treatment weakness and reduced mobility in the elderly. Copyright © 2018 the authors 0270-6474/18/384610-11$15.00/0.

Stereological analysis of sciatic nerve in chickens following neonatal pinealectomy: an experimental study

PubMed Central

2010-01-01

Background Although the injury to the peripheral nervous system is a common clinical problem, understanding of the role of melatonin in nerve degeneration and regeneration is incomplete. Methods The current study investigated the effects of neonatal pinealectomy on the sciatic nerve microarchitecture in the chicken. The chickens were divided into two equal groups: unpinealectomized controls and pinealectomized chickens. At the end of the study, biochemical examination of 10 sciatic nerve samples from both groups was performed and a quantitative stereological evaluation of 10 animals in each group was performed. The results were compared using Mann-Whitney test. Results In this study, the results of axon number and thickness of the myelin sheath of a nerve fiber in newly hatched pinealectomy group were higher than those in control group. Similarly, surgical pinealectomy group had significantly larger axonal cross-sectional area than the control group (p < 0.05). In addition, the average hydroxyproline content of the nerve tissue in neonatal pinealectomy group was higher than those found in control group. Our results suggest that melatonin may play a role on the morphologic features of the peripheral nerve tissue and that melatonin deficiency might be a pathophysiological mechanism in some degenerative diseases of peripheral nerves. The changes demonstrated by quantitative morphometric methods and biochemical analysis has been interpreted as a reflection of the effects of melatonin upon nerve tissue. Conclusion In the light of these results from present animal study, changes in sciatic nerve morphometry may be indicative of neuroprotective feature of melatonin, but this suggestion need to be validated in the human setting. PMID:20409336

Scanning the periphery.

PubMed

Day, George S; Schoemaker, Paul J H

2005-11-01

Companies often face new rivals, technologies, regulations, and other environmental changes that seem to come out of left field. How can they see these changes sooner and capitalize on them? Such changes often begin as weak signals on what the authors call the periphery, or the blurry zone at the edge of an organization's vision. As with human peripheral vision, these signals are difficult to see and interpret but can be vital to success or survival. Unfortunately, most companies lack a systematic method for determining where on the periphery they should be looking, how to interpret the weak signals they see, and how to allocate limited scanning resources. This article provides such a method-a question-based framework for helping companies scan the periphery more efficiently and effectively. The framework divides questions into three categories: learning from the past (What have been our past blind spots? What instructive analogies do other industries offer? Who in the industry is skilled at picking up weak signals and acting on them?); evaluating the present (What important signals are we rationalizing away? What are our mavericks, outliers, complainers, and defectors telling us? What are our peripheral customers and competitors really thinking?); and envisioning the future (What future surprises could really hurt or help us? What emerging technologies could change the game? Is there an unthinkable scenario that might disrupt our business?). Answering these questions is a good first step toward anticipating problems or opportunities that may appear on the business horizon. The article concludes with a self-test that companies can use to assess their need and capability for peripheral vision.

Peripheral KV7 channels regulate visceral sensory function in mouse and human colon.

PubMed

Peiris, Madusha; Hockley, James Rf; Reed, David E; Smith, Ewan St John; Bulmer, David C; Blackshaw, L Ashley

2017-01-01

Background Chronic visceral pain is a defining symptom of many gastrointestinal disorders. The K V 7 family (K V 7.1-K V 7.5) of voltage-gated potassium channels mediates the M current that regulates excitability in peripheral sensory nociceptors and central pain pathways. Here, we use a combination of immunohistochemistry, gut-nerve electrophysiological recordings in both mouse and human tissues, and single-cell qualitative real-time polymerase chain reaction of gut-projecting sensory neurons, to investigate the contribution of peripheral K V 7 channels to visceral nociception. Results Immunohistochemical staining of mouse colon revealed labelling of K V 7 subtypes (K V 7.3 and K V 7.5) with CGRP around intrinsic enteric neurons of the myenteric plexuses and within extrinsic sensory fibres along mesenteric blood vessels. Treatment with the K V 7 opener retigabine almost completely abolished visceral afferent firing evoked by the algogen bradykinin, in agreement with significant co-expression of mRNA transcripts by single-cell qualitative real-time polymerase chain reaction for KCNQ subtypes and the B 2 bradykinin receptor in retrogradely labelled extrinsic sensory neurons from the colon. Retigabine also attenuated responses to mechanical stimulation of the bowel following noxious distension (0-80 mmHg) in a concentration-dependent manner, whereas the K V 7 blocker XE991 potentiated such responses. In human bowel tissues, K V 7.3 and K V 7.5 were expressed in neuronal varicosities co-labelled with synaptophysin and CGRP, and retigabine inhibited bradykinin-induced afferent activation in afferent recordings from human colon. Conclusions We show that K V 7 channels contribute to the sensitivity of visceral sensory neurons to noxious chemical and mechanical stimuli in both mouse and human gut tissues. As such, peripherally restricted K V 7 openers may represent a viable therapeutic modality for the treatment of gastrointestinal pathologies.

Temporally flexible feedback signal to foveal cortex for peripheral object recognition

PubMed Central

Fan, Xiaoxu; Wang, Lan; Shao, Hanyu; Kersten, Daniel; He, Sheng

2016-01-01

Recent studies have shown that information from peripherally presented images is present in the human foveal retinotopic cortex, presumably because of feedback signals. We investigated this potential feedback signal by presenting noise in fovea at different object–noise stimulus onset asynchronies (SOAs), whereas subjects performed a discrimination task on peripheral objects. Results revealed a selective impairment of performance when foveal noise was presented at 250-ms SOA, but only for tasks that required comparing objects’ spatial details, suggesting a task- and stimulus-dependent foveal processing mechanism. Critically, the temporal window of foveal processing was shifted when mental rotation was required for the peripheral objects, indicating that the foveal retinotopic processing is not automatically engaged at a fixed time following peripheral stimulation; rather, it occurs at a stage when detailed information is required. Moreover, fMRI measurements using multivoxel pattern analysis showed that both image and object category-relevant information of peripheral objects was represented in the foveal cortex. Taken together, our results support the hypothesis of a temporally flexible feedback signal to the foveal retinotopic cortex when discriminating objects in the visual periphery. PMID:27671651

Treatment of human immunodeficiency virus-related peripheral neuropathy with Scrambler Therapy: a case report.

PubMed

Smith, Thomas J; Auwaerter, Paul; Knowlton, Amy; Saylor, Deanna; McArthur, Justin

2017-02-01

Peripheral neuropathy is one of the most common neurological complications of HIV infection with a 30-60% lifetime prevalence. Newer HIV drugs cause less peripheral neuropathy, but patients are now living long enough to develop concomitant diabetes-related, vascular-related, and chemotherapy-related neuropathy so it continues as a major debilitating issue. Recent national CDC guidelines have stressed the importance of non-opioid therapies, especially in this population that may have had drug abuse problems. We treated a 52-year-old man who had severe disabling classic peripheral neuropathy since 1998 with Scrambler Therapy (Calmare), an FDA-cleared peripheral non-invasive neuromodulation device. His pain rapidly improved, as did his motor and sensory function, with just four 45-min treatments, and he was able to come off opioids for the first time in years. When his pain returned six months later, only two treatments were needed to resolve it. This represents the first published use of this novel, inexpensive, and non-invasive pain modality in HIV peripheral neuropathy, and should engender further trials.

Cardiovascular effects of simulated zero-gravity in humans

NASA Astrophysics Data System (ADS)

Bonde-Petersen, F.; Suzuki, Y.; Sadámoto, T.; Juel Christensen, N.

Head-down and heat-up tilted bedrest (5 degrees) and head out water immersion (HOWI) for 6 hr were compared. Parameters: Cardiac output (rebreathing method), blood pressure (arm cuff), forearm blood flow (venous occlusion plethysmography), total peripheral (TPR), and forearm vascular (FVR) resistances, Hct, Hb, relativē plasma volume (PV) changes, and plasma catecholamines (single-isotope assay). During HOWI there was as expected a decrement in TPR, FVR, Mean arterial pressure (MAP, from 100 to 80 mmHg), Hct, and PV, and—as a new finding—catecholamines, which were 30-50% lower compared with both + 5 and - 5 degrees bedrest. During head down tilt, MAP was elevated (to 100-110 mmHg) and catecholamines did not fall, while TPR and FVR slowly decreased over 6 hr. HOWI is a stronger stimulus than - 5 degrees bedrest, probably because HOWI elevates central venous pressure more markedly emptying the peripheral veins, while bedrest permits a distension of veins, which induces an increase in sympathetic nervous activity.

Expression levels of seven candidate genes in human peripheral blood mononuclear cells and their association with preeclampsia

PubMed Central

Garza-Veloz, I.; Carrillo-Sanchez, K.; Martinez-Gaytan, V.; Cortes-Flores, R.; Ochoa-Torres, M. A.; Guerrero, G. G.; Rodriguez-Sanchez, I. P.; Cancela-Murrieta, C. O.; Zamudio-Osuna, M.; Badillo-Almaraz, J. I.; Castruita-De la Rosa, C.

2014-01-01

Objective To evaluate the peripheral blood mononuclear cell (PBMC) expression levels of hemeoxygenase 1 (HMOX-1), superoxide dismutase 1 (SOD-1), vascular endothelial growth factor A (VEGF-A), transforming growth factor beta 1 (TGF-β1), interleukin (IL)-6, IL-15 and AdipoQ genes to study their association with preeclampsia (PE). Methods A total of 177 pregnant women were recruited: 108 cases and 69 controls. Quantification of gene expression was measured by quantitative real-time polymerase chain reaction (PCR) using TaqMan probes. Results Underexpression of VEGF-A and TGF-β1 was a constant in most of the cases (80.91% and 76.36%, respectively) and their expression was associated with onset and/or severity of disease (p values < 0.05). IL-6, IL-15 and AdipoQ, showed low or no expression in PBMC samples evaluated. Conclusion PBMC underexpression of VEGF-A and TGF-β1 is a hallmark of PE in the study population. PMID:24295154

Detection of the KIT D816V mutation in peripheral blood of systemic mastocytosis: diagnostic implications.

PubMed

Jara-Acevedo, Maria; Teodosio, Cristina; Sanchez-Muñoz, Laura; Álvarez-Twose, Ivan; Mayado, Andrea; Caldas, Carolina; Matito, Almudena; Morgado, José M; Muñoz-González, Javier I; Escribano, Luis; Garcia-Montero, Andrés C; Orfao, Alberto

2015-08-01

Recent studies have found the KIT D816V mutation in peripheral blood of virtually all adult systemic mastocytosis patients once highly sensitive PCR techniques were used; thus, detection of the KIT D816V mutation in peripheral blood has been proposed to be included in the diagnostic work-up of systemic mastocytosis algorithms. However, the precise frequency of the mutation, the biological significance of peripheral blood-mutated cells and their potential association with involvement of bone marrow hematopoietic cells other than mast cells still remain to be investigated. Here, we determined the frequency of peripheral blood involvement by the KIT D816V mutation, as assessed by two highly sensitive PCR methods, and investigated its relationship with multilineage involvement of bone marrow hematopoiesis. Overall, our results confirmed the presence of the KIT D816V mutation in peripheral blood of most systemic mastocytosis cases (161/190; 85%)--with an increasing frequency from indolent systemic mastocytosis without skin lesions (29/44; 66%) to indolent systemic mastocytosis with skin involvement (124/135; 92%), and more aggressive disease subtypes (11/11; 100%)--as assessed by the allele-specific oligonucleotide-qPCR method, which was more sensitive (P<.0001) than the peptide nucleic acid-mediated PCR approach (84/190; 44%). Although the presence of the KIT mutation in peripheral blood, as assessed by the allele-specific oligonucleotide-qPCR technique, did not accurately predict for multilineage bone marrow involvement of hematopoiesis, the allele-specific oligonucleotide-qPCR allele burden and the peptide nucleic acid-mediated-PCR approach did. These results suggest that both methods provide clinically useful and complementary information through the identification and/or quantification of the KIT D816V mutation in peripheral blood of patients suspected of systemic mastocytosis.

Use of sensitive methods for detection of DNA damage on human lymphocytes exposed to p,p'-DDT: Comet assay and new criteria for scoring micronucleus test.

PubMed

Gajski, Goran; Ravlic, Sanda; Capuder, Zeljka; Garaj-Vrhovac, Vera

2007-08-01

Wide distribution, stability and long persistence in the environment of dichlorodiphenyltrichloroethane (DDT), probably the best-known and most useful insecticide in the world, imposes the need for further examination of the effect of this chemical on human health and especially on the human genome. In this study, peripheral blood human lymphocytes from a healthy donor were exposed to 0.025 mg/L concentration of p,p'-DDT at different time periods (1, 2, 24 and 48 h). For the assessment of genotoxic effect, the new criteria for scoring micronucleus test and alkaline comet assay were used. Both methods showed that p,p'-DDT induces DNA damage in low concentration used in this research. Results of micronucleus test showed a statistically significant (p < 0.05) genotoxic effect of p,p'-DDT on human lymphocytes compared with corresponding control and a different exposure time. A comet assay also showed increased DNA damage caused in p,p'-DDT-exposed human lymphocytes than in corresponding control cells for the tail length. Results obtained by measuring the level of DNA migration and incidence of micronuclei (MN), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) indicate the sensitivity of these tests and their application in detection of primary genome damage after long-term exposure to establish the effect of p,p'-DDT on human genome.

A flow cytometry-based strategy to identify and express IgM from VH1-69+ clonal peripheral B cells.

PubMed

Charles, Edgar D; Orloff, Michael I M; Dustin, Lynn B

2011-01-05

Pathologic rheumatoid factor (RF) levels are hallmarks of several human diseases. Production of monoclonal RF in vitro is essential for studies of the antigenic specificities of RF, as well as for a dissection of the mechanisms of aberrant RF+ B cell activation. We have expanded upon previous methods to develop a flow cytometry-based method to efficiently clone monoclonal antibodies (mAbs) from humans with expansions of RF-like, immunoglobulin heavy chain variable region (IgVH) 1-69 gene segment-containing B cells. The cloned variable regions are expressed as IgM and produced during culture at concentrations between 5 and 20 μg/ml. Using this system, we show that clonal Igs from patients with HCV-related mixed cryoglobulinemia, when expressed as IgM, have RF activity. We anticipate that this system will be useful for the cloning and expression of mAbs partially encoded by VH1-69 and for determination of the reactivity patterns of polyspecific, low-affinity IgMs of human pathogenic importance. Copyright © 2010 Elsevier B.V. All rights reserved.

Thimble microscope system

NASA Astrophysics Data System (ADS)

Kamal, Tahseen; Rubinstein, Jaden; Watkins, Rachel; Cen, Zijian; Kong, Gary; Lee, W. M.

2016-12-01

Wearable computing devices, e.g. Google Glass, Smart watch, embodies the new human design frontier, where technology interfaces seamlessly with human gestures. During examination of any subject in the field (clinic, surgery, agriculture, field survey, water collection), our sensory peripherals (touch and vision) often go hand-in-hand. The sensitivity and maneuverability of the human fingers are guided with tight distribution of biological nerve cells, which perform fine motor manipulation over a range of complex surfaces that is often out of sight. Our sight (or naked vision), on the other hand, is generally restricted to line of sight that is ill-suited to view around corner. Hence, conventional imaging methods are often resort to complex light guide designs (periscope, endoscopes etc) to navigate over obstructed surfaces. Using modular design strategies, we constructed a prototype miniature microscope system that is incorporated onto a wearable fixture (thimble). This unique platform allows users to maneuver around a sample and take high resolution microscopic images. In this paper, we provide an exposition of methods to achieve a thimble microscopy; microscope lens fabrication, thimble design, integration of miniature camera and liquid crystal display.

Photoacoustic and ultrasound dual-modality imaging of human peripheral joints

NASA Astrophysics Data System (ADS)

Xu, Guan; Rajian, Justin R.; Girish, Gandikota; Kaplan, Mariana J.; Fowlkes, J. Brian; Carson, Paul L.; Wang, Xueding

2013-01-01

A photoacoustic (PA) and ultrasound (US) dual modality system, for imaging human peripheral joints, is introduced. The system utilizes a commercial US unit for both US control imaging and PA signal acquisition. Preliminary in vivo evaluation of the system, on normal volunteers, revealed that this system can recover both the structural and functional information of intra- and extra-articular tissues. Confirmed by the control US images, the system, on the PA mode, can differentiate tendon from surrounding soft tissue based on the endogenous optical contrast. Presenting both morphological and pathological information in joint, this system holds promise for diagnosis and characterization of inflammatory joint diseases such as rheumatoid arthritis.

Chromosome instability on children with asthma.

PubMed

Lialiaris, Theodore; Polyzou, Aggeliki; Mpountoukas, Panagiotis; Tsiggene, Anthi; Kouskoukis, Alexandros; Pouliliou, Stamatia; Paraskakis, Emmanouil; Tentes, Ioannis; Trypsianis, Grigorios; Chatzimichail, Athanasios

2009-10-01

Asthma is a complex disease with multiple interactions between genetic and environmental factors. The aim of our study was to investigate the possible genetic instability in asthmatic patients (AP) with asthma in human cultured peripheral blood lymphocytes. Furthermore, the presence of either cytostaticity or cytotoxicity was demonstrated. Human peripheral blood lymphocytes were cultured from 18 admitted children to the Pediatric Clinic of the University Hospital of Alexandroupolis (average age 7.2 years), and 9 healthy blood donors were used as control subjects (average age 6.5 years), none of whom was receiving drugs for medical or other reasons. A significant (p < 0.05) increase in spontaneous sister chromatid exchanges (SCEs) frequency in asthmatic patients compared with control subjects was observed. No statistically significant modification in the spontaneous proliferation rate index (PRI) in AP compared with the controls was demonstrated. Finally, MMC induced a statistically significant increase in SCEs frequency both to controls and to AP, with the MMC-induced SCEs rates in AP being statistically (p < 0.01) higher compared to the MMC-induced SCEs in controls. We try to improve a new diagnostic process of possible genetic instability by a combination of genotoxic, cytostatic and cytotoxic effects of asthma on human peripheral lymphocytes.

The Epigenetic Link between Prenatal Adverse Environments and Neurodevelopmental Disorders

PubMed Central

Kundakovic, Marija; Jaric, Ivana

2017-01-01

Prenatal adverse environments, such as maternal stress, toxicological exposures, and viral infections, can disrupt normal brain development and contribute to neurodevelopmental disorders, including schizophrenia, depression, and autism. Increasing evidence shows that these short- and long-term effects of prenatal exposures on brain structure and function are mediated by epigenetic mechanisms. Animal studies demonstrate that prenatal exposure to stress, toxins, viral mimetics, and drugs induces lasting epigenetic changes in the brain, including genes encoding glucocorticoid receptor (Nr3c1) and brain-derived neurotrophic factor (Bdnf). These epigenetic changes have been linked to changes in brain gene expression, stress reactivity, and behavior, and often times, these effects are shown to be dependent on the gestational window of exposure, sex, and exposure level. Although evidence from human studies is more limited, gestational exposure to environmental risks in humans is associated with epigenetic changes in peripheral tissues, and future studies are required to understand whether we can use peripheral biomarkers to predict neurobehavioral outcomes. An extensive research effort combining well-designed human and animal studies, with comprehensive epigenomic analyses of peripheral and brain tissues over time, will be necessary to improve our understanding of the epigenetic basis of neurodevelopmental disorders. PMID:28335457

Disease associated prion protein may deposit in the peripheral nervous system in human transmissible spongiform encephalopathies.

PubMed

Hainfellner, J A; Budka, H

1999-11-01

There is increasing evidence indicating involvement of the peripheral nervous system (PNS) in the pathogenesis of transmissible spongiform encephalopathies (TSEs). Immunocytochemically detectable deposits of TSE-specific abnormal prion protein (PrP(sc)) are considered as a surrogate marker for infectivity. We used anti-PrP immunocytochemistry to trace PrP(sc) deposition in spinal and enteric ganglia, and peripheral nerve in Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker disease (GSS), and fatal familial insomnia. Discrete PrP(sc) deposits were detectable only in a few posterior root nerve fibers in an adaxonal location in one of nine CJD and the one GSS patients examined. Follicular dendritic cells of the gut and enteric nervous system were not labeled. Thus, PrP(sc) may spread to the PNS in different forms of human prion disease. In contrast to our observations in experimental scrapie (Groschup et al., Acta Neuropathol, this issue), the deposits were scant. Possible explanations for this discrepancy comprise strain difference, or centripetal (experimental scrapie) versus centrifugal (sporadic and genetic human prion diseases) spread of PrP(sc), resulting in different patterns and amounts of PrP(sc) accumulation in the PNS.

Novel Immunohistochemical Techniques Using Discrete Signal Amplification Systems for Human Cutaneous Peripheral Nerve Fiber Imaging

PubMed Central

Wang, Ningshan; Gibbons, Christopher H.; Freeman, Roy

2011-01-01

Confocal imaging uses immunohistochemical binding of specific antibodies to visualize tissues, but technical obstacles limit more widespread use of this technique in the imaging of peripheral nerve tissue. These obstacles include same-species antibody cross-reactivity and weak fluorescent signals of individual and co-localized antigens. The aims of this study were to develop new immunohistochemical techniques for imaging of peripheral nerve fibers. Three-millimeter punch skin biopsies of healthy individuals were fixed, frozen, and cut into 50-µm sections. Tissues were stained with a variety of antibody combinations with two signal amplification systems, streptavidin-biotin-fluorochrome (sABC) and tyramide-horseradish peroxidase-fluorochrome (TSA), used simultaneously to augment immunohistochemical signals. The combination of the TSA and sABC amplification systems provided the first successful co-localization of sympathetic adrenergic and sympathetic cholinergic nerve fibers in cutaneous human sweat glands and vasomotor and pilomotor systems. Primary antibodies from the same species were amplified individually without cross-reactivity or elevated background interference. The confocal fluorescent signal-to-noise ratio increased, and image clarity improved. These modifications to signal amplification systems have the potential for widespread use in the study of human neural tissues. PMID:21411809

Regional assessment of energy-producing metabolic activity in the endothelium of donor corneas.

PubMed

Greiner, Mark A; Burckart, Kimberlee A; Wagoner, Michael D; Schmidt, Gregory A; Reed, Cynthia R; Liaboe, Chase A; Flamme-Wiese, Miles J; Zimmerman, M Bridget; Mullins, Robert F; Kardon, Randy H; Goins, Kenneth M; Aldrich, Benjamin T

2015-05-01

We characterized mitochondrial respiration and glycolysis activity of human corneal endothelium, and compared metabolic activity between central and peripheral regions. Endothelial keratoplasty-suitable corneas were obtained from donors aged 50 to 75 years. The endothelium-Descemet membrane complex (EDM) was isolated, and 3-mm punches were obtained from central and peripheral regions. Endothelium-Descemet membrane punches were assayed for mitochondrial respiration (oxygen consumption) and glycolysis (extracellular acidification) using an extracellular flux analyzer. Enzymatic (citrate synthase, glucose hexokinase) and mitochondrial density (MitoTracker) assays also were performed. Ten corneas were analyzed per assay. Metabolic activity for mitochondrial respiration and glycolysis showed expected changes to assay compounds (P < 0.01, all pairwise comparisons). Basal mitochondrial respiration and glycolysis activity did not differ between regions (P > 0.99). Similarly, central versus peripheral activity after assay compound treatment showed no significant differences (P > 0.99, all time points). The intracorneal coefficient of variation for basal readings between two and four peripheral punches was 18.5% of the mean. Although peripheral samples displayed greater enzymatic activity than central samples (P < 0.05), similar to extracellular flux results, mitochondrial density did not differ between regions (P = 0.78). Extracellular flux analysis of oxygen and pH is a valid technique for characterizing metabolic activity of human corneal endothelium. This technique demonstrates high reproducibility, allows quantification of metabolic parameters using small quantities of live cells, and permits estimation of overall metabolic output. Neither oxygen consumption nor extracellular acidification differed between central and peripheral regions of transplant suitable corneas in this series. Our results show that endothelial cell health can be quantified biochemically in transplant suitable corneas.

Chronic recording of hand prosthesis control signals via a regenerative peripheral nerve interface in a rhesus macaque

NASA Astrophysics Data System (ADS)

Irwin, Z. T.; Schroeder, K. E.; Vu, P. P.; Tat, D. M.; Bullard, A. J.; Woo, S. L.; Sando, I. C.; Urbanchek, M. G.; Cederna, P. S.; Chestek, C. A.

2016-08-01

Objective. Loss of even part of the upper limb is a devastating injury. In order to fully restore natural function when lacking sufficient residual musculature, it is necessary to record directly from peripheral nerves. However, current approaches must make trade-offs between signal quality and longevity which limit their clinical potential. To address this issue, we have developed the regenerative peripheral nerve interface (RPNI) and tested its use in non-human primates. Approach. The RPNI consists of a small, autologous partial muscle graft reinnervated by a transected peripheral nerve branch. After reinnervation, the graft acts as a bioamplifier for descending motor commands in the nerve, enabling long-term recording of high signal-to-noise ratio (SNR), functionally-specific electromyographic (EMG) signals. We implanted nine RPNIs on separate branches of the median and radial nerves in two rhesus macaques who were trained to perform cued finger movements. Main results. No adverse events were noted in either monkey, and we recorded normal EMG with high SNR (>8) from the RPNIs for up to 20 months post-implantation. Using RPNI signals recorded during the behavioral task, we were able to classify each monkey’s finger movements as flexion, extension, or rest with >96% accuracy. RPNI signals also enabled functional prosthetic control, allowing the monkeys to perform the same behavioral task equally well with either physical finger movements or RPNI-based movement classifications. Significance. The RPNI signal strength, stability, and longevity demonstrated here represents a promising method for controlling advanced prosthetic limbs and fully restoring natural movement.

Chronic recording of hand prosthesis control signals via a regenerative peripheral nerve interface in a rhesus macaque.

PubMed

Irwin, Z T; Schroeder, K E; Vu, P P; Tat, D M; Bullard, A J; Woo, S L; Sando, I C; Urbanchek, M G; Cederna, P S; Chestek, C A

2016-08-01

Loss of even part of the upper limb is a devastating injury. In order to fully restore natural function when lacking sufficient residual musculature, it is necessary to record directly from peripheral nerves. However, current approaches must make trade-offs between signal quality and longevity which limit their clinical potential. To address this issue, we have developed the regenerative peripheral nerve interface (RPNI) and tested its use in non-human primates. The RPNI consists of a small, autologous partial muscle graft reinnervated by a transected peripheral nerve branch. After reinnervation, the graft acts as a bioamplifier for descending motor commands in the nerve, enabling long-term recording of high signal-to-noise ratio (SNR), functionally-specific electromyographic (EMG) signals. We implanted nine RPNIs on separate branches of the median and radial nerves in two rhesus macaques who were trained to perform cued finger movements. No adverse events were noted in either monkey, and we recorded normal EMG with high SNR (>8) from the RPNIs for up to 20 months post-implantation. Using RPNI signals recorded during the behavioral task, we were able to classify each monkey's finger movements as flexion, extension, or rest with >96% accuracy. RPNI signals also enabled functional prosthetic control, allowing the monkeys to perform the same behavioral task equally well with either physical finger movements or RPNI-based movement classifications. The RPNI signal strength, stability, and longevity demonstrated here represents a promising method for controlling advanced prosthetic limbs and fully restoring natural movement.

Pharmacoethnicity in Paclitaxel-Induced Sensory Peripheral Neuropathy

PubMed Central

Komatsu, Masaaki; Wheeler, Heather E.; Chung, Suyoun; Low, Siew-Kee; Wing, Claudia; Delaney, Shannon M.; Gorsic, Lidija K.; Takahashi, Atsushi; Kubo, Michiaki; Kroetz, Deanna L.; Zhang, Wei; Nakamura, Yusuke; Dolan, M. Eileen

2015-01-01

Purpose Paclitaxel is used worldwide in the treatment of breast, lung, ovarian and other cancers. Sensory peripheral neuropathy is an associated adverse effect that cannot be predicted, prevented or mitigated. To better understand the contribution of germline genetic variation to paclitaxel-induced peripheral neuropathy, we undertook an integrative approach that combines genome-wide association study (GWAS) data generated from HapMap lymphoblastoid cell lines (LCLs) and Asian patients. Methods GWAS was performed with paclitaxel-induced cytotoxicity generated in 363 LCLs and with paclitaxel-induced neuropathy from 145 Asian patients. A gene-based approach was used to identify overlapping genes and compare to a European clinical cohort of paclitaxel-induced neuropathy. Neurons derived from human induced pluripotent stem cells were used for functional validation of candidate genes. Results SNPs near AIPL1 were significantly associated with paclitaxel-induced cytotoxicity in Asian LCLs (P < 10−6). Decreased expression of AIPL1 resulted in decreased sensitivity of neurons to paclitaxel by inducing neurite morphological changes as measured by increased relative total outgrowth, number of processes and mean process length. Using a gene-based analysis, there were 32 genes that overlapped between Asian LCL cytotoxicity and Asian patient neuropathy (P < 0.05) including BCR. Upon BCR knockdown, there was an increase in neuronal sensitivity to paclitaxel as measured by neurite morphological characteristics. Conclusion We identified genetic variants associated with Asian paclitaxel-induced cytotoxicity and functionally validated the AIPL1 and BCR in a neuronal cell model. Furthermore, the integrative pharmacogenomics approach of LCL/patient GWAS may help prioritize target genes associated with chemotherapeutic-induced peripheral neuropathy. PMID:26015512

The Impact of Glyphosate, Its Metabolites and Impurities on Viability, ATP Level and Morphological changes in Human Peripheral Blood Mononuclear Cells

PubMed Central

Kwiatkowska, Marta; Jarosiewicz, Paweł; Michałowicz, Jaromir; Koter-Michalak, Maria; Huras, Bogumiła; Bukowska, Bożena

2016-01-01

The toxicity of herbicides to animals and human is an issue of worldwide concern. The present study has been undertaken to assess toxic effect of widely used pesticide—glyphosate, its metabolites: aminomethylphosphonic acid (AMPA) and methylphosphonic acid and its impurities: N-(phosphonomethyl)iminodiacetic acid (PMIDA), N-methylglyphosate, hydroxymethylphosphonic acid and bis-(phosphonomethyl)amine on human peripheral blood mononuclear cells (PBMCs). We have evaluated the effect of those compounds on viability, ATP level, size (FSC-A parameter) and granulation (SSC-A parameter) of the cells studied. Human peripheral blood mononuclear cells were exposed to different concentrations of glyphosate, its metabolites and impurities (0.01–10 mM) for 4 and 24 h. It was found that investigated compounds caused statistically significant decrease in viability and ATP level of PBMCs. The strongest changes in cell viability and ATP level were observed after 24 h incubation of PBMCs with bis-(phosphonomethyl)amine, and particularly PMIDA. Moreover, all studied compounds changed cell granularity, while PMIDA and bis-(phosphonomethyl)amine altered PBMCs size. It may be concluded that bis-(phosphonomethyl)amine, and PMIDA caused a slightly stronger damage to PBMCs than did glyphosate. Changes in the parameters studied in PBMCs were observed only at high concentrations of the compounds examined, which clearly shows that they may occur in this cell type only as a result of acute poisoning of human organism with these substances. PMID:27280764

Burn-related peripheral neuropathy: A systematic review.

PubMed

Tu, Yiji; Lineaweaver, William C; Zheng, Xianyou; Chen, Zenggan; Mullins, Fred; Zhang, Feng

2017-06-01

Peripheral neuropathy is the most frequent disabling neuromuscular complication of burns. However, the insidious and progressive onset of burn neuropathy makes it often undiagnosed or overlooked. In our study, we reviewed the current studies on the burn-related peripheral neuropathy to summarize the morbidity, mechanism, detecting method and management of peripheral neuropathy in burn patients. Of the 1533 burn patients included in our study, 98 cases (6.39%) were presented with peripheral neuropathy. Thermal and electrical burns were the most common etiologies. Surgical procedures, especially nerve decompression, showed good effect on functional recovery of both acute and delayed peripheral neuropathy in burn patients. It is noteworthy that, for early detection and prevention of peripheral neuropathy, electrodiagnostic examinations should be performed on burn patients independent of symptoms. Still, the underlying mechanisms of burn-related peripheral neuropathy remain to be clarified. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Evaluation of tissue components in the peripheral nervous system using Sirius red staining and immunohistochemistry: a comparative study (human, pig, rat).

PubMed

Kaemmer, D; Bozkurt, A; Otto, J; Junge, K; Klink, C; Weis, J; Sellhaus, B; O'Dey, D M; Pallua, N; Jansen, M; Schumpelick, V; Klinge, U

2010-06-30

Little is known about species differences in the peripheral nerve system and quantitative evaluation of main tissue components has rarely been done. Nevertheless, animal models are used for example in pain research without exact knowledge of degree of fibrosis in pathological states which would determine possible treatment options. It would therefore be of crucial interest to describe the degree of fibrosis and the remaining functional nerve tissue as exact as possible. In the present study we evaluated collagen (stroma) and nerve fiber (parenchyma) composition of peripheral nerves in three species (human, rat, pig) and used digital colour-separation and analysis for collagen type differentiation and quantification of immuno-positive-stained area. We found similar ratios of collagen types I and III in epineurium and similar immuno-positive area for staining of neurofilament and S-100beta. In contrast, we measured significantly different ratios of collagen type I to type III in the endoneurium. This combined analysis of the main tissue components of peripheral nerves could be an easy-to-use tool in evaluating changes during damage caused by scaring, systemic disease or compression syndromes. The calculated collagen type I/III ratio may serve as an objective diagnostic value for the description or as prognostic marker for therapeutic approaches in peripheral nerve pathology. However, in particular studies of collagen accumulation in nerves, species dependant differences have to be considered. Copyright 2010 Elsevier B.V. All rights reserved.

Arsenic exposure from drinking water is associated with decreased gene expression and increased DNA methylation in peripheral blood

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ameer, Syeda Shegufta

Background: Exposure to inorganic arsenic increases the risk of cancer and non-malignant diseases. Inefficient arsenic metabolism is a marker for susceptibility to arsenic toxicity. Arsenic may alter gene expression, possibly by altering DNA methylation. Objectives: To elucidate the associations between arsenic exposure, gene expression, and DNA methylation in peripheral blood, and the modifying effects of arsenic metabolism. Methods: The study participants, women from the Andes, Argentina, were exposed to arsenic via drinking water. Arsenic exposure was assessed as the sum of arsenic metabolites in urine (U-As), using high performance liquid-chromatography hydride-generation inductively-coupled-plasma-mass-spectrometry, and arsenic metabolism efficiency was assessed by themore » urinary fractions (%) of the individual metabolites. Genome-wide gene expression (N = 80 women) and DNA methylation (N = 93; 80 overlapping with gene expression) in peripheral blood were measured using Illumina DirectHyb HumanHT-12 v4.0 and Infinium Human-Methylation 450K BeadChip, respectively. Results: U-As concentrations, ranging 10–1251 μg/L, was associated with decreased gene expression: 64% of the top 1000 differentially expressed genes were down-regulated with increasing U-As. U-As was also associated with hypermethylation: 87% of the top 1000 CpGs were hypermethylated with increasing U-As. The expression of six genes and six individual CpG sites were significantly associated with increased U-As concentration. Pathway analyses revealed enrichment of genes related to cell death and cancer. The pathways differed somewhat depending on arsenic metabolism efficiency. We found no overlap between arsenic-related gene expression and DNA methylation for individual genes. Conclusions: Increased arsenic exposure was associated with lower gene expression and hypermethylation in peripheral blood, but with no evident overlap. - Highlights: • Women exposed to inorganic arsenic were studied for molecular responses in blood. • Arsenic is associated with decreased gene expression and increased DNA methylation. • Arsenic related pathways differed to some extent due to arsenic metabolism efficiency.« less

Virtual screening and biological evaluation of piperazine derivatives as human acetylcholinesterase inhibitors.

PubMed

Varadaraju, Kavitha Raj; Kumar, Jajur Ramanna; Mallesha, Lingappa; Muruli, Archana; Mohana, Kikkeri Narasimha Shetty; Mukunda, Chethan Kumar; Sharanaiah, Umesha

2013-01-01

The piperazine derivatives have been shown to inhibit human acetylcholinesterase. Virtual screening by molecular docking of piperazine derivatives 1-(1,4-benzodioxane-2-carbonyl) piperazine (K), 4-(4-methyl)-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S1), and 4-(4-chloro)-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S3) has been shown to bind at peripheral anionic site and catalytic sites, whereas 4-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S4) and 4-(2,5-dichloro)-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S7) do not bind either to peripheral anionic site or catalytic site with hydrogen bond. All the derivatives have differed in number of H-bonds and hydrophobic interactions. The peripheral anionic site interacting molecules have proven to be potential therapeutics in inhibiting amyloid peptides aggregation in Alzheimer's disease. All the piperazine derivatives follow Lipinski's rule of five. Among all the derivatives 1-(1,4-benzodioxane-2-carbonyl) piperazine (K) was found to have the lowest TPSA value.

Virtual Screening and Biological Evaluation of Piperazine Derivatives as Human Acetylcholinesterase Inhibitors

PubMed Central

Varadaraju, Kavitha Raj; Kumar, Jajur Ramanna; Mallesha, Lingappa; Muruli, Archana; Mohana, Kikkeri Narasimha Shetty; Mukunda, Chethan Kumar; Sharanaiah, Umesha

2013-01-01

The piperazine derivatives have been shown to inhibit human acetylcholinesterase. Virtual screening by molecular docking of piperazine derivatives 1-(1,4-benzodioxane-2-carbonyl) piperazine (K), 4-(4-methyl)-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S1), and 4-(4-chloro)-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S3) has been shown to bind at peripheral anionic site and catalytic sites, whereas 4-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S4) and 4-(2,5-dichloro)-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S7) do not bind either to peripheral anionic site or catalytic site with hydrogen bond. All the derivatives have differed in number of H-bonds and hydrophobic interactions. The peripheral anionic site interacting molecules have proven to be potential therapeutics in inhibiting amyloid peptides aggregation in Alzheimer's disease. All the piperazine derivatives follow Lipinski's rule of five. Among all the derivatives 1-(1,4-benzodioxane-2-carbonyl) piperazine (K) was found to have the lowest TPSA value. PMID:24288651

Expression profiling feline peripheral blood monocytes identifies a transcriptional signature associated with type two diabetes mellitus.

PubMed

O'Leary, Caroline A; Sedhom, Mamdouh; Reeve-Johnson, Mia; Mallyon, John; Irvine, Katharine M

2017-04-01

Diabetes mellitus is a common disease of cats and is similar to type 2 diabetes (T2D) in humans, especially with respect to the role of obesity-induced insulin resistance, glucose toxicity, decreased number of pancreatic β-cells and pancreatic amyloid deposition. Cats have thus been proposed as a valuable translational model of T2D. In humans, inflammation associated with adipose tissue is believed to be central to T2D development, and peripheral blood monocytes (PBM) are important in the inflammatory cascade which leads to insulin resistance and β-cell failure. PBM may thus provide a useful window to study the pathogenesis of diabetes mellitus in cats, however feline monocytes are poorly characterised. In this study, we used the Affymetrix Feline 1.0ST array to profile peripheral blood monocytes from 3 domestic cats with T2D and 3 cats with normal glucose tolerance. Feline monocytes were enriched for genes expressed in human monocytes, and, despite heterogeneous gene expression, we identified a T2D-associated expression signature associated with cell cycle perturbations, DNA repair and the unfolded protein response, oxidative phosphorylation and inflammatory responses. Our data provide novel insights into the feline monocyte transcriptome, and support the hypothesis that inflammatory monocytes contribute to T2D pathogenesis in cats as well as in humans. Copyright © 2017 Elsevier B.V. All rights reserved.

Visual brain plasticity induced by central and peripheral visual field loss.

PubMed

Sanda, Nicolae; Cerliani, Leonardo; Authié, Colas N; Sabbah, Norman; Sahel, José-Alain; Habas, Christophe; Safran, Avinoam B; Thiebaut de Schotten, Michel

2018-06-23

Disorders that specifically affect central and peripheral vision constitute invaluable models to study how the human brain adapts to visual deafferentation. We explored cortical changes after the loss of central or peripheral vision. Cortical thickness (CoTks) and resting-state cortical entropy (rs-CoEn), as a surrogate for neural and synaptic complexity, were extracted in 12 Stargardt macular dystrophy, 12 retinitis pigmentosa (tunnel vision stage), and 14 normally sighted subjects. When compared to controls, both groups with visual loss exhibited decreased CoTks in dorsal area V3d. Peripheral visual field loss also showed a specific CoTks decrease in early visual cortex and ventral area V4, while central visual field loss in dorsal area V3A. Only central visual field loss exhibited increased CoEn in LO-2 area and FG1. Current results revealed biomarkers of brain plasticity within the dorsal and the ventral visual streams following central and peripheral visual field defects.

Analysis of the peripheral immune response in patients with neurocysticercosis: evidence for T cell reactivity to parasite glycoprotein and vesicular fluid antigens.

PubMed

Restrepo, B I; Aguilar, M I; Melby, P C; Teale, J M

2001-10-01

In neurocysticercosis (NCC), it is thought that the long-term survival of the parasite within the human brain is due in part to the ability of the cestode to suppress the local immune response. When the parasite dies, the immunosuppression is apparently lost and a strong local inflammatory response then develops. In contrast, little is known about the immunologic response that may occur in the peripheral immune system of these patients. In this study, the status of the peripheral (extracerebral) cellular and humoral response was evaluated in patients with a history of NCC. The in vitro proliferation of peripheral blood mononuclear cells to mitogens and foreign antigens was similar in patients and controls. Importantly, a substantive response was elicited by two Taenia solium metacestode antigens. In addition, 8 of 10 patients had a detectable humoral response to the antigenic glycoproteins of the cestode. Considering both the cellular and humoral response, all of the patients with NCC presented an active peripheral immunity.

Prodromal disease: Immune responses of the host macrophage system to humoral factors

NASA Technical Reports Server (NTRS)

Criswell, B. S.; Knight, V.

1973-01-01

A composite is presented of nine studies, each yielding information contributing toward an understanding of methods designed to detect disease during the prodromal stages. The data further point to new areas of study that might be useful in early diagnoses. Five of the none experiments were done in mice. Four of these involved acute infectious disease states and one involved a chronic autoimmune type disease. Of the numerous perimeters studied of the acute diseases, the uptake of H3- thymidine by peripheral blood lymphocytes appeared to yield the earliest indication of disease. This test was not useful in studying the chronic disease state. Four of the nine studies involved application of diagnostic technics to human disease. A normal baseline for H3-thymidine incorporation by human lymphocytes was determined. A subject with severe combined immunodeficiency disease was studied. A human volunteer study was done using Influenza A live attenuated vaccine. Finally, a human volunteer study of subjects infected with Influenza A was done.

Electrophysiological measurements of diabetic peripheral neuropathy: A systematic review.

PubMed

Shabeeb, Dheyauldeen; Najafi, Masoud; Hasanzadeh, Gholamreza; Hadian, Mohammed Reza; Musa, Ahmed Eleojio; Shirazi, Alireza

2018-03-28

Peripheral neuropathy is one of the main complications of diabetes mellitus. One of the features of diabetic nerve damage is abnormality of sensory and motor nerve conduction study. An electrophysiological examination can be reproduced and is also a non-invasive approach in the assessment of peripheral nerve function. Population-based and clinical studies have been conducted to validate the sensitivity of these methods. When the diagnosis was based on clinical electrophysiological examination, abnormalities were observed in all patients. In this research, using a review design, we reviewed the issue of clinical electrophysiological examination of diabetic peripheral neuropathy in articles from 2008 to 2017. For this purpose, PubMed, Scopus and Embase databases of journals were used for searching articles. The researchers indicated that diabetes (both types) is a very disturbing health issue in the modern world and should be given serious attention. Based on conducted studies, it was demonstrated that there are different procedures for prevention and treatment of diabetes-related health problems such as diabetic polyneuropathy (DPN). The first objective quantitative indication of the peripheral neuropathy is abnormality of sensory and motor nerve conduction tests. Electrophysiology is accurate, reliable and sensitive. It can be reproduced and also is a noninvasive approach in the assessment of peripheral nerve function. The methodological review has found that the best method for quantitative indication of the peripheral neuropathy compared with all other methods is clinical electrophysiological examination. For best results, standard protocols such as temperature control and equipment calibration are recommended. Copyright © 2018. Published by Elsevier Ltd.

Rapid CD4+ T-Cell Loss Induced by Human Immunodeficiency Virus Type 1NC in Uninfected and Previously Infected Chimpanzees

PubMed Central

Novembre, Francis J.; de Rosayro, Juliette; Nidtha, Soumya; O'Neil, Shawn P.; Gibson, Terri R.; Evans-Strickfaden, Tammy; Hart, Clyde E.; McClure, Harold M.

2001-01-01

To investigate the pathogenicity of a virus originating in a chimpanzee with AIDS (C499), two chimpanzees were inoculated with a plasma-derived isolate termed human immunodeficiency virus type 1NC (HIV-1NC). A previously uninfected chimpanzee, C534, experienced rapid peripheral CD4+ T-cell loss to fewer than 26 cells/μl by 14 weeks after infection. CD4+ T-cell depletion was associated with high plasma HIV-1 loads but a low virus burden in the peripheral lymph node. The second chimpanzee, C459, infected 13 years previously with HIV-1LAV, experienced a more protracted course of peripheral CD4+ T-cell loss after HIV-1NC inoculation, resulting in fewer than 200 cells/μl by 96 weeks postinoculation. The quantities of viral RNA in the plasma and peripheral lymph node from C459 were below the lower limits of detection prior to inoculation with HIV-1NC but were significantly and persistently increased after superinfection, with HIV-1NC representing the predominant viral genotype. These results show that viruses derived from C499 are more pathogenic for chimpanzees than any other HIV-1 isolates described to date. PMID:11152525

Analysis of IL-2-like factor in lymphocyte culture supernatant of olive flounder, Paralichthys oliveaceus

NASA Astrophysics Data System (ADS)

Wu, Riqin; Zhang, Peijun; Li, Jun; Xu, Yongli

2005-03-01

To study immune mechanism of fish lymphocyte we performed a proliferation assay and ELISA using monoclonal antibody against human IL-2. The result showed that an interleukin-2 (IL-2)-like factor was detected in the supernatant of plant haemoglutinin (PHA)-stimulated lymphocyte culture from peripheral blood, spleen and head kidney of olive flounder, Paralichthys olivaceus. The quantities of IL-2-like factor in the supernatant from different lymphoid tissues were quite different. The IL-2 like factor in the supernatant from cultured head kidney lymphocytes was much higher than those of peripheral blood lymphocytes and spleen lymphocytes ( P<0.01). The IL-2 activity was found in either mouse thymocyte proliferation assay or flounder head kidney lymphocyte proliferation assay and shown to have obvious enhancing effect on proliferation of the above two types of cell. The recombinant human IL-2, (rhIL-2) was able to stimulate flounder thymocyte proliferation and used to detect the IL-2 receptor (IL-2R) on the surface of flounder lymphocyte. The cross-reaction between the lymphocytes of flounder peripheral blood and CD25(IL-2R) was detected with flow cytometry and shown that the percentage of CD25-positive cell in peripheral blood was 7.74±0.67%.

Arginase activity in peripheral blood of patients with intestinal schistosomiasis, Wonji, Central Ethiopia.

PubMed

Getaneh, A; Tamrat, A; Tadesse, K

2015-07-01

Morbidity and mortality caused by schistosomiasis usually results from immunopathology. But the underlying mechanisms are not yet clearly understood. Th2-type immune response is thought to be dominant during chronic schistosomiasis, and upregulation of arginase-I is one component of this milieu. A cohort study was conducted to assess arginase activity in peripheral blood of humans with intestinal schistosomiasis in Wonji-Shoa Sugar Estate, Central Ethiopia. Laboratory-confirmed 30 Schistosoma mansoni-infected patients and 18 apparently healthy controls were recruited. Faecal egg count was carried out by Kato-Katz technique. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated from whole blood. Activity of arginase in plasma and PBMC lysates was measured, and results were compared with that of controls. Twenty-one of 30 patients had light infection, whereas moderate and heavy intensity infections were observed in eight and only one patient(s), respectively. A significant increase in both PBMC (patients: 59.96 + 82.99, controls: 25.44 + 24.6 mU/mg protein, P < 0.0001) and plasma (patients: 1.61 + 2.19, controls: 0.31 + 0.73 mU/mL plasma, P < 0.0001) arginase activity was observed during human S. mansoni infection. Arginase activity increases in peripheral blood of patients with intestinal schistosomiasis. © 2015 John Wiley & Sons Ltd.

Use of Nerve Conduction Velocity to Assess Peripheral Nerve Health in Aging Mice

PubMed Central

Walsh, Michael E.; Sloane, Lauren B.; Fischer, Kathleen E.; Austad, Steven N.; Richardson, Arlan

2015-01-01

Nerve conduction velocity (NCV), the speed at which electrical signals propagate along peripheral nerves, is used in the clinic to evaluate nerve function in humans. A decline in peripheral nerve function is associated with a number of age-related pathologies. While several studies have shown that NCV declines with age in humans, there is little information on the effect of age on NCV in peripheral nerves in mice. In this study, we evaluated NCV in male and female C57Bl/6 mice ranging from 4 to 32 months of age. We observed a decline in NCV in both male and female mice after 20 months of age. Sex differences were detected in sensory NCV as well as the rate of decline during aging in motor nerves; female mice had slower sensory NCV and a slower age-related decline in motor nerves compared with male mice. We also tested the effect of dietary restriction on NCV in 30-month-old female mice. Dietary restriction prevented the age-related decline in sciatic NCV but not other nerves. Because NCV is clinically relevant to the assessment of nerve function, we recommend that NCV be used to evaluate healthspan in assessing genetic and pharmacological interventions that increase the life span of mice. PMID:25477428

HEPC-based liposomes trigger cytokine release from peripheral blood cells: effects of liposomal size, dose and lipid composition.

PubMed

Yamamoto, Sayaka; Ishida, Tatsuhiro; Inoue, Akiko; Mikami, Junko; Muraguchi, Masahiro; Ohmoto, Yasukazu; Kiwada, Hiroshi

2002-04-02

The immune response caused by liposome stimulation was studied by assessing the level of several cytokines released from human peripheral blood cells. Liposome stimulation resulted in the release of IL-6, IL-10, IL-1beta, TNF-alpha and IFN-gamma. The size of the liposomes affected the degree of the cytokine releases with larger sized liposomes causing higher levels of cytokine induction. In addition, it appears that the lipid composition of liposomes had no effect on the degree of cytokine release. The release of cytokines occurred even in the absence of serum, suggesting that serum proteins did not contribute to liposome stimulation in peripheral blood cells. The release of cytokines induced by liposome stimulation was inhibited by the presence of either protein kinase-C (PKC) or protein tyrosine kinase (PTK) inhibitor, but not by the presence of an endocytosis inhibitor. This indicates that signal transduction via PKC or PTK is necessary, in order for human peripheral blood cells to release cytokines (IL-6, IL-10, IL-1beta, TNF-alpha and IFN-gamma) as the result of liposome stimulation. These quantitative data on the release of cytokines by liposomal stimulation provide useful information for the development of rational drug delivery systems and the safety of cytokine induction via the use of liposomes.

VIBROTACTILE THRESHOLD AND PIN-PRICK SENSITIVITY AS INDICATORS OF SUBCLINICAL CHANGES IN SOMATOSENSORY FUNCTION: EFFECTS OF ENVIRONMENTAL EXPOSURE TO ARSENIC IN DRINKING WATER.

EPA Science Inventory

Peripheral neuropathy is a classical symptom of arsenic poisoning. Nerve conduction velocity (NCV) is the preferred measure for clinical assessment of peripheral neuropathy, but this method is not practical for field studies. Alternative methods available for assessing functi...

Ultrasound-guided, percutaneous peripheral nerve stimulation: technical note.

PubMed

Chan, Isaac; Brown, Anthony R; Park, Kenneth; Winfree, Christopher J

2010-09-01

Peripheral nerve stimulation is a form of neuromodulation that applies electric current to peripheral nerves to induce stimulation paresthesias within the painful areas. To report a method of ultrasound-guided, percutaneous peripheral nerve stimulation. This technique utilizes real-time imaging to avoid injury to adjacent vascular structures during minimally invasive placement of peripheral nerve stimulator electrodes. We describe a patient that presented with chronic, bilateral foot pain following multiple foot surgeries, for whom a comprehensive, pain management treatment strategy had failed. We utilized ultrasound-guided, percutaneous tibial nerve stimulation at a thigh level to provide durable pain relief on the right side, and open peripheral nerve stimulation on the left. The patient experienced appropriate stimulation paresthesias and excellent pain relief on the plantar aspect of the right foot with the percutaneous electrode. On the left side, we were unable to direct the stimulation paresthesias to the sole of the foot, despite multiple electrode repositionings. A subsequent, open placement of a left tibial nerve stimulator was performed. This revealed that the correct electrode position against the tibial nerve was immediately adjacent to the popliteal artery, and was thus not appropriate for percutaneous placement. We describe a method of ultrasound-guided peripheral nerve stimulation that avoids the invasiveness of electrode placement via an open procedure while providing excellent pain relief. We further describe limitations of the percutaneous approach when navigating close to large blood vessels, a situation more appropriately managed with open peripheral nerve stimulator placement. Ultrasound-guided placement may be considered for patients receiving peripheral nerve stimulators placed within the deep tissues, and not easily placed in a blind fashion.

Atomic resolution view into the structure–function relationships of the human myelin peripheral membrane protein P2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ruskamo, Salla; University of Oulu, Oulu; Yadav, Ravi P.

2014-01-01

The structure of the human myelin peripheral membrane protein P2 has been refined at 0.93 Å resolution. In combination with functional experiments in vitro, in vivo and in silico, the fine details of the structure–function relationships in P2 are emerging. P2 is a fatty acid-binding protein expressed in vertebrate peripheral nerve myelin, where it may function in bilayer stacking and lipid transport. P2 binds to phospholipid membranes through its positively charged surface and a hydrophobic tip, and accommodates fatty acids inside its barrel structure. The structure of human P2 refined at the ultrahigh resolution of 0.93 Å allows detailed structuralmore » analyses, including the full organization of an internal hydrogen-bonding network. The orientation of the bound fatty-acid carboxyl group is linked to the protonation states of two coordinating arginine residues. An anion-binding site in the portal region is suggested to be relevant for membrane interactions and conformational changes. When bound to membrane multilayers, P2 has a preferred orientation and is stabilized, and the repeat distance indicates a single layer of P2 between membranes. Simulations show the formation of a double bilayer in the presence of P2, and in cultured cells wild-type P2 induces membrane-domain formation. Here, the most accurate structural and functional view to date on P2, a major component of peripheral nerve myelin, is presented, showing how it can interact with two membranes simultaneously while going through conformational changes at its portal region enabling ligand transfer.« less

Analysis of HLA-B15 and HLA-B27 in spondyloarthritis with peripheral and axial clinical patterns

PubMed Central

Londono, John; Santos, Ana Maria; Peña, Paola; Calvo, Enrique; Espinosa, Luis R; Reveille, John D; Vargas-Alarcon, Gilberto; Jaramillo, Carlos A; Valle-Oñate, Rafael; Avila, Mabel; Romero, Consuelo; Medina, Juan F

2015-01-01

Objective Human leucocyte antigen (HLA) B27 and HLA-B15 are associated with spondyloarthritis (SpA). Recent Assessment of SpondyloArthritis international Society (ASAS) criteria emphasise a distinction between SpA with axial and peripheral patterns. We analysed whether HLA-A, HLA-B and HLA-DRB1 alleles could associate with these patterns. Methods We studied 100 healthy individuals and 178 patients with SpA according to European Spondyloarthropathy Study Group (ESSG) criteria. Patients were then classified according to ASAS criteria, the axial spondyloarthritis pattern (axSpA) being defined by ascertained sacroiliitis and the peripheral pattern (pSpA) by enthesitis and/or arthritis in extremities. A combined ax/p pattern was also considered. Results Only HLA-B27 and HLA-B15 alleles were associated with SpA. ASAS criteria for axSpA were met in 152 patients (12 with isolated axSpA and 140 with a combined ax/p patterns). When the ASAS peripheral criteria were applied, 161 patients met these criteria (13 with isolated pSpA and 148 with a combined ax/p pattern). HLA-B27 was found in 83% of patients with axSpA and 43% of ax/pSpA patients according to axASAS. HLA-B27 occurred in 7% controls but not in any patient with isolated pSpA. HLA-B15 was encountered in 31% of patients with isolated pSpA and 20% of ax/pSpA patients according to pASAS criteria. Moreover, 2 healthy controls, but none of our patients with isolated axSpA were positive for HLA-B15. Conclusions Our data suggest that the presence of HLA-B15 favours the development of isolated/combined peripheral rather than isolated axSpA, while HLA-B27 promotes an isolated/combined axial disease and excludes a peripheral pattern. HLA-B15 should be considered in addition to HLA-B27 when diagnosing patients with SpA according to ASAS criteria. PMID:26560062

High viral load in lymph nodes and latent human immunodeficiency virus (HIV) in peripheral blood cells of HIV-1-infected chimpanzees.

PubMed Central

Saksela, K; Muchmore, E; Girard, M; Fultz, P; Baltimore, D

1993-01-01

We have examined human immunodeficiency virus type 1 (HIV-1) infection in chimpanzees by analyzing HIV-1 DNA and RNA in lymph nodes and peripheral mononuclear cells (PBMCs). Like certain asymptomatic HIV-infected persons, these chimpanzees had no detectable viral replication in their PBMCs. However, viral replication and a high viral load were observed in the lymphatic tissue. Despite the absence of viral replication in PBMCs, 1/1,000 to 1/10,000 of the PBMCs contained HIV-1 proviral DNA, and HIV transcription could be rapidly induced in these cells in vitro. These results provide direct evidence of cellular latency of HIV in vivo and suggest that HIV infection in chimpanzees may be a useful model for clinical latency of HIV infection in humans. Images PMID:8230463

Hepatobiliary fascioliasis in non-endemic zones: a surprise diagnosis.

PubMed

Jha, Ashish Kumar; Goenka, Mahesh Kumar; Goenka, Usha; Chakrabarti, Amrita

2013-03-01

Fascioliasis is a zoonotic infection caused by Fasciola hepatica. Because of population migration and international food trade, human fascioliasis is being an increasingly recognised entity in nonendemic zones. In most parts of Asia, hepatobiliary fascioliasis is sporadic. Human hepatobiliary infection by this trematode has two distinct phases: an acute hepatic phase and a chronic biliary phase. Hepatobiliary infection is mostly associated with intense peripheral eosinophilia. In addition to classically defined hepatic phase and biliary phase fascioliasis, some cases may have an overlap of these two phases. Chronic liver abscess formation is a rare presentation. We describe a surprise case of hepatobiliary fascioliasis who presented to us with liver abscess without intense peripheral eosinophilia, a rare presentation of human fascioliasis especially in non-endemic zones. Copyright © 2013 Arab Journal of Gastroenterology. Published by Elsevier Ltd. All rights reserved.

[Blood-nerve barrier and peripheral nerve regeneration].

PubMed

Kanda, Takashi

2013-01-01

Blood-nerve barrier (BNB) restricts the movement of soluble mediators and leukocytes from the blood contents to the peripheral nervous system (PNS) parenchyma and thus maintains the endoneurial homeostasis. However, it interferes the supply of various neurotrophic factors from the blood constituents and stops the drainage of toxic substances out of the PNS parenchyma, resulting in the inhibition of peripheral nerve regeneration. If the manipulation of BNB function is possible, regeneration of peripheral nerve may be facilitated via the alteration of peripheral nerve microenvironment and ample supply of neurotrophic substances. A possible method to manipulate the BNB for therapeutic purposes is to modify the endothelial function using siRNAs, oligonucleotides and virus vectors. Another possible method is to modify BNB pericytes: small hydrophobic substances that can reach the pericyte membrane through the endothelial monolayer and strengthen the pericytic activity, including the release of various cytokines/chemokines that influence endothelial function, may also be useful as drug candidates to control the BNB function.

Signal evaluation environment: a new method for the design of peripheral in-vehicle warning signals.

PubMed

Werneke, Julia; Vollrath, Mark

2011-06-01

An evaluation method called the Signal Evaluation Environment (SEE) was developed for use in the early stages of the design process of peripheral warning signals while driving. Accident analyses have shown that with complex driving situations such as intersections, the visual scan strategies of the driver contribute to overlooking other road users who have the right of way. Salient peripheral warning signals could disrupt these strategies and direct drivers' attention towards these road users. To select effective warning signals, the SEE was developed as a laboratory task requiring visual-cognitive processes similar to those used at intersections. For validation of the SEE, four experiments were conducted using different stimulus characteristics (size, colour contrast, shape, flashing) that influence peripheral vision. The results confirm that the SEE is able to differentiate between the selected stimulus characteristics. The SEE is a useful initial tool for designing peripheral signals, allowing quick and efficient preselection of beneficial signals.

Ultrawide-field Fluorescein Angiography for Evaluation of Diabetic Retinopathy

PubMed Central

Kong, Mingui; Lee, Mee Yon

2012-01-01

Purpose To investigate the advantages of ultrawide-field fluorescein angiography (FA) over the standard fundus examination in the evaluation of diabetic retinopathy (DR). Methods Ultrawide-field FAs were obtained in 118 eyes of 59 diabetic patients; 11 eyes with no DR, 71 eyes with nonproliferative diabetic retinopathy (NPDR), and 36 eyes with proliferative diabetic retinopathy (PDR), diagnosed by the standard method. The presence of peripheral abnormal lesions beyond the standard seven fields was examined. Results Ultrawide-field FA images demonstrated peripheral microaneurysms in six (54.5%) of 11 eyes with no DR and all eyes with moderate to severe NPDR and PDR. Peripheral retinal neovascularizations were detected in three (4.2%) of 71 eyes with NPDR and in 13 (36.1%) of 36 eyes with PDR. Peripheral vascular nonperfusion and vascular leakage were found in two-thirds of eyes with severe NPDR and PDR. Conclusions Ultrawide-field FA demonstrates peripheral lesions beyond standard fields, which can allow early detection and a close evaluation of DR. PMID:23204797

Ratio of Circulating IFNγ (+) "Th17 Cells" in Memory Th Cells Is Inversely Correlated with the Titer of Anti-CCP Antibodies in Early-Onset Rheumatoid Arthritis Patients Based on Flow Cytometry Methods of the Human Immunology Project.

PubMed

Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi

2016-01-01

Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic joint inflammation characterized by activated T cells. IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. However, it remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we validated the methods of the Human Immunology Project using only the cell-surface marker through measuring the actual expression of IL-17 and IFNγ. We also evaluated the expression of CD161 in human Th17 cells. We then tried to identify Th17 cells, IL-17(+)Th17 cells, and IFNγ (+)Th17 cells in the peripheral blood of early-onset RA patients using the standardized method of the Human Immunology Project. Our findings validated the method and the expression of CD161. The ratio of IFNγ (+)Th17 cells in memory T cells was inversely correlated to the titers of anti-CCP antibodies in the early-onset RA patients. These findings suggest that Th17 cells play important roles in the early phase of RA and that anti-IL-17 antibodies should be administered to patients with early phase RA, especially those with high titers of CCP antibodies.

Ratio of Circulating IFNγ + “Th17 Cells” in Memory Th Cells Is Inversely Correlated with the Titer of Anti-CCP Antibodies in Early-Onset Rheumatoid Arthritis Patients Based on Flow Cytometry Methods of the Human Immunology Project

PubMed Central

Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi

2016-01-01

Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic joint inflammation characterized by activated T cells. IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. However, it remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we validated the methods of the Human Immunology Project using only the cell-surface marker through measuring the actual expression of IL-17 and IFNγ. We also evaluated the expression of CD161 in human Th17 cells. We then tried to identify Th17 cells, IL-17+Th17 cells, and IFNγ +Th17 cells in the peripheral blood of early-onset RA patients using the standardized method of the Human Immunology Project. Our findings validated the method and the expression of CD161. The ratio of IFNγ +Th17 cells in memory T cells was inversely correlated to the titers of anti-CCP antibodies in the early-onset RA patients. These findings suggest that Th17 cells play important roles in the early phase of RA and that anti-IL-17 antibodies should be administered to patients with early phase RA, especially those with high titers of CCP antibodies. PMID:27294146

Onyx, a New Liquid Embolic Material for Peripheral Interventions: Preliminary Experience in Aneurysm, Pseudoaneurysm, and Pulmonary Arteriovenous Malformation Embolization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vanninen, Ritva L., E-mail: ritva.vanninen@kuh.fi; Manninen, I.

Purpose. To describe our preliminary experience with a new liquid embolization agent, Onyx, in peripheral interventions. Methods and results. We successfully treated two peripheral aneurysms (one in an internal iliac artery, one in a thoracic collateral artery of an aortic coarctation), two peripheral pseudoaneurysms (one in a lumbar artery, one in a renal artery), and one pulmonary arteriovenous malformation. Conclusion. Onyx is a promising alternative embolic material for peripheral interventions. It can be combined with coils in selected cases, and balloon catheters can be effectively used during slow injection of embolic material to control flow and protect the aneurysm neck.

Regarding the quantification of peripheral microcirculation--Comparing responses evoked in the in vivo human lower limb by postural changes, suprasystolic occlusion and oxygen breathing.

PubMed

Silva, Henrique; Ferreira, Hugo; Bujan, Ma Julia; Rodrigues, Luis Monteiro

2015-05-01

The human skin is an interesting model to explore microcirculation, particularly if using noninvasive technologies such as LDF (Laser Doppler Flowmetry) and tc (transcutaneous) gasimetry and methods as near as possible from the normal physiological state. In this study, we combined those technologies with three classical approaches--leg raising from supine, suprasystolic occlusion (in the ankle), and normobaric oxygen breathing to explore distal peripheral circulation in the foot. These methods are often cited, but a comparative assessment has not been done. The goal of this study was to identify relevant flow related descriptors, method-related advantages and pitfalls, and eventually, to find the best experimental approach. Volunteers (both genders, 22.1 ± 3.7 years old) were subjected to these methods and variables registered during basal, challenge and stabilization phases. Descriptive and comparative statistics were obtained, adopting a 95% confidence level. All flow-related quantitative descriptors potentially useful for the analysis were identified and compared. As expected, male patients consistently showed higher LDF levels and transepidermal water loss (TEWL) and lower tcpO2 values. However, lower results were recorded in the supine position, suggesting a postural dependence. Both leg raising and suprasystolic occlusion produced a hyperemic response after provocation, although different in magnitude, significantly reducing LDF and tcpO2 during provocation. The oxygen breathing method provided the most patient-friendly protocol, consistently reducing LDF (potentially by the inhibition of production of local vasodilators). TEWL increased during the provocation phase in all protocols, although not significantly. Baseline tcpO2 was found to correlate positively with the peak tcpO2 during oxygen breathing and basal LDF with peak flow during leg raising and suprasystolic occlusion. No statistical correlation between TEWL and LDF could be demonstrated under the current experimental conditions. We conclude that although equally useful considering the purpose, these methods involve very different practicalities and do not provide the same information. Also noteworthy, LDF is a highly sensitive indicator that could be further explored to look deeper into blood flow regulating mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

Perspectives on Systems Modeling of Human Peripheral Blood Mononuclear Cells

PubMed Central

Sen, Partho; Kemppainen, Esko; Orešič, Matej

2018-01-01

Human peripheral blood mononuclear cells (PBMCs) are the key drivers of the immune responses. These cells undergo activation, proliferation and differentiation into various subsets. During these processes they initiate metabolic reprogramming, which is coordinated by specific gene and protein activities. PBMCs as a model system have been widely used to study metabolic and autoimmune diseases. Herein we review various omics and systems-based approaches such as transcriptomics, epigenomics, proteomics, and metabolomics as applied to PBMCs, particularly T helper subsets, that unveiled disease markers and the underlying mechanisms. We also discuss and emphasize several aspects of T cell metabolic modeling in healthy and disease states using genome-scale metabolic models. PMID:29376056

The effects of lipid A on gamma-irradiated human peripheral blood lymphocytes in vitro

NASA Astrophysics Data System (ADS)

Dubničková, M.; Kuzmina, E. A.; Chausov, V. N.; Ravnachka, I.; Boreyko, A. V.; Krasavin, E. A.

2016-03-01

The modulatory effects of lipid A (diphosphoryl lipid A (DLA) and monophosphoryl lipid A (MLA)) on apoptosis induction and DNA structure damage (single and double-strand breaks (SSBs and DSBs, respectively)) in peripheral human blood lymphocytes are studied for 60Co gamma-irradiation. It is shown that in the presence of these agents the amount of apoptotic cells increases compared with the irradiated control samples. The effect is most strongly pronounced for DLA. In its presence, a significant increase is observed in the number of radiation-induced DNA SSBs and DSBs. Possible mechanisms are discussed of the modifying influence of the used agents on radiation-induced cell reactions

[New methods for the evaluation of bone quality. Assessment of bone structural property using imaging.

PubMed

Ito, Masako

Structural property of bone includes micro- or nano-structural property of the trabecular and cortical bone, and macroscopic geometry. Radiological technique is useful to analyze the bone structural property;multi-detector row CT(MDCT)or high-resolution peripheral QCT(HR-pQCT)is available to analyze human bone in vivo . For the analysis of hip geometry, CT-based hip structure analysis(HSA)is available as well as DXA-based HSA. These structural parameters are related to biomechanical property, and these assessment tools provide information of pathological changes or the effects of anti-osteoporotic agents on bone.

Peripheral nerve hyperexcitability with preterminal nerve and neuromuscular junction remodeling is a hallmark of Schwartz-Jampel syndrome.

PubMed

Bauché, Stéphanie; Boerio, Delphine; Davoine, Claire-Sophie; Bernard, Véronique; Stum, Morgane; Bureau, Cécile; Fardeau, Michel; Romero, Norma Beatriz; Fontaine, Bertrand; Koenig, Jeanine; Hantaï, Daniel; Gueguen, Antoine; Fournier, Emmanuel; Eymard, Bruno; Nicole, Sophie

2013-12-01

Schwartz-Jampel syndrome (SJS) is a recessive disorder with muscle hyperactivity that results from hypomorphic mutations in the perlecan gene, a basement membrane proteoglycan. Analyses done on a mouse model have suggested that SJS is a congenital form of distal peripheral nerve hyperexcitability resulting from synaptic acetylcholinesterase deficiency, nerve terminal instability with preterminal amyelination, and subtle peripheral nerve changes. We investigated one adult patient with SJS to study this statement in humans. Perlecan deficiency due to hypomorphic mutations was observed in the patient biological samples. Electroneuromyography showed normal nerve conduction, neuromuscular transmission, and compound nerve action potentials while multiple measures of peripheral nerve excitability along the nerve trunk did not detect changes. Needle electromyography detected complex repetitive discharges without any evidence for neuromuscular transmission failure. The study of muscle biopsies containing neuromuscular junctions showed well-formed post-synaptic element, synaptic acetylcholinesterase deficiency, denervation of synaptic gutters with reinnervation by terminal sprouting, and long nonmyelinated preterminal nerve segments. These data support the notion of peripheral nerve hyperexcitability in SJS, which would originate distally from synergistic actions of peripheral nerve and neuromuscular junction changes as a result of perlecan deficiency. Copyright © 2013 Elsevier B.V. All rights reserved.

Role of Schwann cells in the regeneration of penile and peripheral nerves

PubMed Central

Wang, Lin; Sanford, Melissa T; Xin, Zhongcheng; Lin, Guiting; Lue, Tom F

2015-01-01

Schwann cells (SCs) are the principal glia of the peripheral nervous system. The end point of SC development is the formation of myelinating and nonmyelinating cells which ensheath large and small diameter axons, respectively. They play an important role in axon regeneration after injury, including cavernous nerve injury that leads to erectile dysfunction (ED). Despite improvement in radical prostatectomy surgical techniques, many patients still suffer from ED postoperatively as surgical trauma causes traction injuries and local inflammatory changes in the neuronal microenvironment of the autonomic fibers innervating the penis resulting in pathophysiological alterations in the end organ. The aim of this review is to summarize contemporary evidence regarding: (1) the origin and development of SCs in the peripheral and penile nerve system; (2) Wallerian degeneration and SC plastic change following peripheral and penile nerve injury; (3) how SCs promote peripheral and penile nerve regeneration by secreting neurotrophic factors; (4) and strategies targeting SCs to accelerate peripheral nerve regeneration. We searched PubMed for articles related to these topics in both animal models and human research and found numerous studies suggesting that SCs could be a novel target for treatment of nerve injury-induced ED. PMID:25999359

Idiopathic hirsutism: local and peripheral expression of aromatase (CYP19A) and 5α-reductase genes (SRD5A1 and SRD5A2).

PubMed

Caglayan, A Okay; Dundar, Munis; Tanriverdi, Fatih; Baysal, Nuran A; Unluhizarci, Kursad; Ozkul, Yusuf; Borlu, Murat; Batukan, Cem; Kelestimur, Fahrettin

2011-08-01

To evaluate idiopathic hirsutism etiology via molecular studies testing peripheral and local aromatase and 5α-reductase expression. Assessment of the expression of messenger RNA (mRNA) for type 1 and 2,5α-reductase isoenzyme gene (SDR5A1, SDR5A2) and aromatase (CYP19A) in dermal papillae cells and peripheral blood mononuclear cells. University hospital. 28 untreated idiopathic hirsute patients and 20 healthy women (controls). Human skin biopsies and peripheral venous blood. SDR5A1, SDR5A2, CYP19A gene expression in skin biopsies and peripheral blood. A statistically significant reduction of SRD5A1, SRD5A2, and CYP19A gene expression was found in the dermal papillae cells and peripheral blood mononuclear cell between the study and control group. Further study, including protein expression and enzyme activity assays, are warranted to characterize the paradoxically low gene expression levels of local 5α-reductase and aromatase in women with idiopathic hirsutism. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Dose-Response Curves of the FDXR and RAD51 Genes with 6 and 18 MV Beam Energies in Human Peripheral Blood Lymphocytes.

PubMed

Saberi, Alihossein; Khodamoradi, Ehsan; Tahmasebi Birgani, Mohammad Javad; Makvandi, Manoochehr; Noori, Bijan

2016-11-01

Rapid dose assessment using biological dosimetry methods is essential to increase the chance of survival of exposed individuals in radiation accidents. We compared the expression levels of the FDXR and RAD51 genes at 6 and 18 MV beam energies in human peripheral blood lymphocytes. The results of our study can be used to analyze radiation energy in biological dosimetry. For this in vitro experimental study, from 36 students in the medical physics and virology departments, seven voluntary, healthy, non-smoking male blood donors of Khuzestan ethnicity with no history of exposure to ionization radiation were selected using simple randomized sampling. Sixty-three peripheral blood samples were collected from the seven healthy donors. Human peripheral blood was then exposed to doses of 0, 0.2, 0.5, 2, and 4 Gy with 6 and 18 MV beam energies in a Linac Varian 2100C/D (Varian, USA) at Golestan hospital in Ahvaz, Iran. After RNA extraction and cDNA synthesis, the expression levels of FDXR and RAD51 were determined 24 hours post-irradiation using the gel-purified reverse transcription polymerase chain reaction (RT-PCR) technique and TaqMan strategy (by real-time PCR). The expression level of FDXR gene was significantly increased at doses of 2 Gy and 4 Gy in the 6 - 18 MV energy range (P < 0.001 and P < 0.008, respectively). The medians with interquartile ranges (IQRs) of the copy numbers of the FDXR gene at 2 Gy and 4 Gy doses under 6 and 18 MV beam energies were 2393.59 (1798.21, 2575.37) and 2983.00 (2199.48, 3643.82) and 3779.12 (3051.40, 5120.74) and 5051.26 (4704.83, 5859.17), respectively. However, RAD51 gene expression levels only showed a significant difference between samples at a dose of 2 Gy with 6 and 18 MV beam energies, respectively (P < 0.040). The medians with IQRs of the copy numbers of the RAD51 gene were 2092.77 (1535.78, 2705.61) and 3412.57 (2979.72, 4530.61) at beam energies of 6 and 18 MV, respectively. The data suggest that the expression analysis of the FDXR gene, contrary to that of the RAD51 gene, may be suitable for assessment of high-energy X-ray. In addition, RAD51 is not a suitable gene for dose assessment in biological dosimetry.

Autoradiographic analysis of binding sites for sup 125 I-Bolton-Hunter-substance P in the human eye

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kieselbach, G.F.; Ragaut, R.; Knaus, H.G.

1990-07-01

Substance P is known to exert potent effects in peripheral tissues, and is thought to be important for ocular function. The mechanism of action of substance P in the human eye is not known. As a basis for biochemical characterization specific binding of {sup 125}I-Bolton-Hunter-substance P was demonstrated in the human eye using autoradiographic methods. Biochemical characterization on slide-mounted tissue preparations showed that binding was saturable with a KD of 0.27 +/- 0.1 nmol/l. Specific binding occurred at comparable autoradiographic densities to both human retina and choroid. Substance P and its carboxyterminal fragment, substance P(3-11), were shown to be highlymore » potent in binding competition experiments against {sup 125}I-Bolton-Hunter-substance P. Similar concentrations of substance P(1-9), neurokinin A and neurokinin B failed to significantly alter specific binding of {sup 125}I-Bolton-Hunter-substance P. The results indicate expression of high affinity substance P binding sites in human retina and choroid.« less

Phenotypic and Genetic Characterization of Circulating Tumor Cells by Combining Immunomagnetic Selection and FICTION Techniques

PubMed Central

Campos, María; Prior, Celia; Warleta, Fernando; Zudaire, Isabel; Ruíz-Mora, Jesús; Catena, Raúl; Calvo, Alfonso; Gaforio, José J.

2008-01-01

The presence of circulating tumor cells (CTCs) in breast cancer patients has been proven to have clinical relevance. Cytogenetic characterization of these cells could have crucial relevance for targeted cancer therapies. We developed a method that combines an immunomagnetic selection of CTCs from peripheral blood with the fluorescence immunophenotyping and interphase cytogenetics as a tool for investigation of neoplasm (FICTION) technique. Briefly, peripheral blood (10 ml) from healthy donors was spiked with a predetermined number of human breast cancer cells. Nucleated cells were separated by double density gradient centrifugation of blood samples. Tumor cells (TCs) were immunomagnetically isolated with an anti-cytokeratin antibody and placed onto slides for FICTION analysis. For immunophenotyping and genetic characterization of TCs, a mixture of primary monoclonal anti-pancytokeratin antibodies was used, followed by fluorescent secondary antibodies, and finally hybridized with a TOP2A/HER-2/CEP17 multicolor probe. Our results show that TCs can be efficiently isolated from peripheral blood and characterized by FICTION. Because genetic amplification of TOP2A and ErbB2 (HER-2) in breast cancer correlates with response to anthracyclines and herceptin therapies, respectively, this novel methodology could be useful for a better classification of patients according to the genetic alterations of CTCs and for the application of targeted therapies. (J Histochem Cytochem 56:667–675, 2008) PMID:18413646

ASGR1 and ASGR2, the Genes that Encode the Asialoglycoprotein Receptor (Ashwell Receptor), Are Expressed in Peripheral Blood Monocytes and Show Interindividual Differences in Transcript Profile

PubMed Central

Harris, Rebecca Louise; van den Berg, Carmen Wilma; Bowen, Derrick John

2012-01-01

Background. The asialoglycoprotein receptor (ASGPR) is a hepatic receptor that mediates removal of potentially hazardous glycoconjugates from blood in health and disease. The receptor comprises two proteins, asialoglycoprotein receptor 1 and 2 (ASGR1 and ASGR2), encoded by the genes ASGR1 and ASGR2. Design and Methods. Using reverse transcription amplification (RT-PCR), expression of ASGR1 and ASGR2 was investigated in human peripheral blood monocytes. Results. Monocytes were found to express ASGR1 and ASGR2 transcripts. Correctly spliced transcript variants encoding different isoforms of ASGR1 and ASGR2 were present in monocytes. The profile of transcript variants from both ASGR1 and ASGR2 differed among individuals. Transcript expression levels were compared with the hepatocyte cell line HepG2 which produces high levels of ASGPR. Monocyte transcripts were 4 to 6 orders of magnitude less than in HepG2 but nonetheless readily detectable using standard RT-PCR. The monocyte cell line THP1 gave similar results to monocytes harvested from peripheral blood, indicating it may provide a suitable model system for studying ASGPR function in this cell type. Conclusions. Monocytes transcribe and correctly process transcripts encoding the constituent proteins of the ASGPR. Monocytes may therefore represent a mobile pool of the receptor, capable of reaching sites remote from the liver. PMID:22919488

Associations of Fatty Acids in Cerebrospinal Fluid with Peripheral Glucose Concentrations and Energy Metabolism

PubMed Central

Jumpertz, Reiner; Guijarro, Ana; Pratley, Richard E.; Mason, Clinton C.; Piomelli, Daniele; Krakoff, Jonathan

2012-01-01

Rodent experiments have emphasized a role of central fatty acid (FA) species, such as oleic acid, in regulating peripheral glucose and energy metabolism. Thus, we hypothesized that central FAs are related to peripheral glucose regulation and energy expenditure in humans. To test this we measured FA species profiles in cerebrospinal fluid (CSF) and plasma of 32 individuals who stayed in our clinical inpatient unit for 6 days. Body composition was measured by dual energy X-ray absorptiometry and glucose regulation by an oral glucose test (OGTT) followed by measurements of 24 hour (24EE) and sleep energy expenditure (SLEEP) as well as respiratory quotient (RQ) in a respiratory chamber. CSF was obtained via lumbar punctures; FA concentrations were measured by liquid chromatography/mass spectrometry. As expected, FA concentrations were higher in plasma compared to CSF. Individuals with high concentrations of CSF very-long-chain saturated FAs had lower rates of SLEEP. In the plasma moderate associations of these FAs with higher 24EE were observed. Moreover, CSF monounsaturated long-chain FA (palmitoleic and oleic acid) concentrations were associated with lower RQs and lower glucose area under the curve during the OGTT. Thus, FAs in the CSF strongly correlated with peripheral metabolic traits. These physiological parameters were most specific to long-chain monounsaturated (C16∶1, C18∶1) and very-long-chain saturated (C24∶0, C26∶0) FAs. Conclusions: Together with previous animal experiments these initial cross-sectional human data indicate that central FA species are linked to peripheral glucose and energy homeostasis. PMID:22911803

Contact area affects frequency-dependent responses to vibration in the peripheral vascular and sensorineural systems.

PubMed

Krajnak, Kristine; Miller, G R; Waugh, Stacey

2018-01-01

Repetitive exposure to hand-transmitted vibration is associated with development of peripheral vascular and sensorineural dysfunctions. These disorders and symptoms associated with it are referred to as hand-arm vibration syndrome (HAVS). Although the symptoms of the disorder have been well characterized, the etiology and contribution of various exposure factors to development of the dysfunctions are not well understood. Previous studies performed using a rat-tail model of vibration demonstrated that vascular and peripheral nervous system adverse effects of vibration are frequency-dependent, with vibration frequencies at or near the resonant frequency producing the most severe injury. However, in these investigations, the amplitude of the exposed tissue was greater than amplitude typically noted in human fingers. To determine how contact with vibrating source and amplitude of the biodynamic response of the tissue affects the risk of injury occurring, this study compared the influence of frequency using different levels of restraint to assess how maintaining contact of the tail with vibrating source affects the transmission of vibration. Data demonstrated that for the most part, increasing the contact of the tail with the platform by restraining it with additional straps resulted in an enhancement in transmission of vibration signal and elevation in factors associated with vascular and peripheral nerve injury. In addition, there were also frequency-dependent effects, with exposure at 250 Hz generating greater effects than vibration at 62.5 Hz. These observations are consistent with studies in humans demonstrating that greater contact and exposure to frequencies near the resonant frequency pose the highest risk for generating peripheral vascular and sensorineural dysfunction.

Linking neuronal brain activity to the glucose metabolism

PubMed Central

2013-01-01

Background Energy homeostasis ensures the functionality of the entire organism. The human brain as a missing link in the global regulation of the complex whole body energy metabolism is subject to recent investigation. The goal of this study is to gain insight into the influence of neuronal brain activity on cerebral and peripheral energy metabolism. In particular, the tight link between brain energy supply and metabolic responses of the organism is of interest. We aim to identifying regulatory elements of the human brain in the whole body energy homeostasis. Methods First, we introduce a general mathematical model describing the human whole body energy metabolism. It takes into account the two central roles of the brain in terms of energy metabolism. The brain is considered as energy consumer as well as regulatory instance. Secondly, we validate our mathematical model by experimental data. Cerebral high-energy phosphate content and peripheral glucose metabolism are measured in healthy men upon neuronal activation induced by transcranial direct current stimulation versus sham stimulation. By parameter estimation we identify model parameters that provide insight into underlying neurophysiological processes. Identified parameters reveal effects of neuronal activity on regulatory mechanisms of systemic glucose metabolism. Results Our examinations support the view that the brain increases its glucose supply upon neuronal activation. The results indicate that the brain supplies itself with energy according to its needs, and preeminence of cerebral energy supply is reflected. This mechanism ensures balanced cerebral energy homeostasis. Conclusions The hypothesis of the central role of the brain in whole body energy homeostasis as active controller is supported. PMID:23988084

[Food Addiction as a new behavioral addiction].

PubMed

Eördögh, Erika; Hoyer, Mária; Szeleczky, Gábor

Aim of review: To overview the new studies on food addiction and highlighting the analogies and differences between food and drug addiction. Recent studies on food addiction have demonstrated that the neurobiological circuits involved in the development of drug addiction also play a role in food consumption, and that the uptake of nutrients by the organism is under the control of numerous complicated peripheral and central signal-transducing networks. In addition, it has also been shown that addiction and/or craving may develop toward certain foods and nutrients, too. The most recent investigations about the neurobiological systems motivating the obtaining behavior have suggested that the acquired drive toward energy rich, rewarding food contributes to the appearance of obesity as an endemic. This report presents the definition of substance use disorders and describes the results of the neurobiological approaches in the study of addiction supporting the concept that food addiction is a real phenomenon. The subsequent description of the central and peripheral signaling pathways of food consumption demonstrates that while both food (nutrients) and drugs with abuse potential exert their effect on the same central neurobiological networks, the action of the peripheral signaling systems make it more difficult to understand the regulation of food intake and thus the treatment of pathological eating behavior. The presentation of the evidences of food addiction obtained in animal experiments and with imaging methods and the subsequent overview of the results achieved in the surveys of pathologic eating patterns and in the new clinical and behavioral assessment of human food addiction point to the conclusion that the pharmacological and behavioral therapy methods applied to the treatment of substance abuse disorders may also prove useful in the management of obesity.

Expression of NMDA receptor subunits in human blood lymphocytes: A peripheral biomarker in online computer game addiction.

PubMed

Sadat-Shirazi, Mitra-Sadat; Vousooghi, Nasim; Alizadeh, Bentolhoda; Makki, Seyed Mohammad; Zarei, Seyed Zeinolabedin; Nazari, Shahrzad; Zarrindast, Mohammad Reza

2018-05-23

Background and aims Repeated performance of some behaviors such as playing computer games could result in addiction. The NMDA receptor is critically involved in the development of behavioral and drug addictions. It has been claimed that the expression level of neurotransmitter receptors in the brain may be reflected in peripheral blood lymphocytes (PBLs). Methods Here, using a real-time PCR method, we have investigated the mRNA expression of GluN2A, GluN2D, GluN3A, and GluN3B subunits of the NMDA receptor in PBLs of male online computer game addicts (n = 25) in comparison with normal subjects (n = 26). Results Expression levels of GluN2A, GluN2D, and GluN3B subunits were not statistically different between game addicts and the control group. However, the mRNA expression of the GluN3A subunit was downregulated in PBLs of game addicts. Discussion and conclusions Transcriptional levels of GluN2A and GluN2D subunits in online computer game addicts are similar to our previously reported data of opioid addiction and are not different from the control group. However, unlike our earlier finding of drug addiction, the mRNA expression levels of GluN3A and GluN3B subunits in PBLs of game addicts are reduced and unchanged, respectively, compared with control subjects. It seems that the downregulated state of the GluN3A subunit of NMDA receptor in online computer game addicts is a finding that deserves more studies in the future to see whether it can serve as a peripheral biomarker in addiction studies, where the researcher wants to rule out the confusing effects of abused drugs.

Evaluation of Macaca mulatta as a model for genotoxicity studies.

PubMed

Dobrovolsky, Vasily N; Shaddock, Joseph G; Mittelstaedt, Roberta A; Manjanatha, Mugimane G; Miura, Daishiro; Uchikawa, Makoto; Mattison, Donald R; Morris, Suzanne M

2009-02-19

We have investigated the use of peripheral blood from the nonhuman primate (NHP) rhesus monkey (Macaca mulatta) as a model system for mutation detection. The rhesus monkey is metabolically closer to humans than most common laboratory animals, and therefore may be a relevant model for hazard identification and human risk assessment. To validate the model, conditions were determined for in vitro selection and expansion of 6-thioguanine-resistant (6-TGr) HPRT mutant and proaerolysin-resistant (ProAERr) PIG-A mutant lymphocytes from peripheral blood obtained by routine venipuncture. Also, flow cytometric methods were developed for the rapid detection of PIG-A mutant erythrocytes. The flow cytometric analysis of PIG-A mutant erythrocytes was based on enumerating cells deficient in surface markers attached to the cellular membrane via glycosylphosphatidyl inositol (GPI) anchors. Mutant cells were enumerated over an extended period of time in peripheral blood of male monkeys receiving daily doses of the electrolyte replenisher Prangtrade mark (a common carrier for oral delivery of drugs in NHPs), and in the blood of one male monkey treated with a single i.p. dose of 50mg/kg of N-ethyl-N-nitrosourea at approximately 2 years of age and another similar injection at approximately 3.5 years of age. The spontaneous PIG-A and HPRT T-cell mutant frequency (MF) was low in animals receiving Prang (0-8x10(-6)), and treatment with ENU resulted in a clearly detectable increase in the frequency of ProAERr and 6-TGr lymphocytes (up to approximately 28x10(-6) and approximately 30x10(-6), respectively). Also, the ENU-treated animal had higher frequency of GPI-deficient erythrocytes (46.5x10(-6) in the treated animal vs. 7.8+/-4.2x10(-6) in control animals). Our results indicate that the rhesus monkey can be a valuable model for the identification of agents that may impact upon human health as mutagens and that the PIG-A gene can be a useful target for detection of mutation in both white and red blood cells.

Integrated versus nOn-integrated Peripheral inTravenous catheter. Which Is the most effective systeM for peripheral intravenoUs catheter Management? (The OPTIMUM study): a randomised controlled trial protocol

PubMed Central

Castillo, Maria Isabel; Larsen, Emily; Cooke, Marie; Marsh, Nicole M; Wallis, Marianne C; Finucane, Julie; Brown, Peter; Mihala, Gabor; Byrnes, Joshua; Walker, Rachel; Cable, Prudence; Zhang, Li; Sear, Candi; Jackson, Gavin; Rowsome, Anna; Ryan, Alison; Humphries, Julie C; Sivyer, Susan; Flanigan, Kathy; Rickard, Claire M

2018-01-01

Introduction Peripheral intravenous catheters (PIVCs) are frequently used in hospitals. However, PIVC complications are common, with failures leading to treatment delays, additional procedures, patient pain and discomfort, increased clinician workload and substantially increased healthcare costs. Recent evidence suggests integrated PIVC systems may be more effective than traditional non-integrated PIVC systems in reducing phlebitis, infiltration and costs and increasing functional dwell time. The study aim is to determine the efficacy, cost–utility and acceptability to patients and professionals of an integrated PIVC system compared with a non-integrated PIVC system. Methods and analysis Two-arm, multicentre, randomised controlled superiority trial of integrated versus non-integrated PIVC systems to compare effectiveness on clinical and economic outcomes. Recruitment of 1560 patients over 2 years, with randomisation by a centralised service ensuring allocation concealment. Primary outcomes: catheter failure (composite endpoint) for reasons of: occlusion, infiltration/extravasation, phlebitis/thrombophlebitis, dislodgement, localised or catheter-associated bloodstream infections. Secondary outcomes: first time insertion success, types of PIVC failure, device colonisation, insertion pain, functional dwell time, adverse events, mortality, cost–utility and consumer acceptability. One PIVC per patient will be included, with intention-to-treat analysis. Baseline group comparisons will be made for potentially clinically important confounders. The proportional hazards assumption will be checked, and Cox regression will test the effect of group, patient, device and clinical variables on failure. An as-treated analysis will assess the effect of protocol violations. Kaplan-Meier survival curves with log-rank tests will compare failure by group over time. Secondary endpoints will be compared between groups using parametric/non-parametric techniques. Ethics and dissemination Ethical approval from the Royal Brisbane and Women’s Hospital Human Research Ethics Committee (HREC/16/QRBW/527), Griffith University Human Research Ethics Committee (Ref No. 2017/002) and the South Metropolitan Health Services Human Research Ethics Committee (Ref No. 2016–239). Results will be published in peer-reviewed journals. Trial registration number ACTRN12617000089336. PMID:29764876

Methods Development for Blood Borne Macrophage Carriage of Nanoformulated Antiretroviral Drugs

PubMed Central

Roy, Upal; Martinez-Skinner, Andrea; McMillan, JoEllyn; Gendelman, Howard E.

2010-01-01

Nanoformulated drugs can improve pharmacodynamics and bioavailability while serving also to reduce drug toxicities for antiretroviral (ART) medicines. To this end, our laboratory has applied the principles of nanomedicine to simplify ART regimens and as such reduce toxicities while improving compliance and drug pharmacokinetics. Simple and reliable methods for manufacturing nanoformulated ART (nanoART) are shown. Particles of pure drug are encapsulated by a thin layer of surfactant lipid coating and produced by fractionating larger drug crystals into smaller ones by either wet milling or high-pressure homogenization. In an alternative method free drug is suspended in a droplet of a polymer. Herein, drug is dissolved within a polymer then agitated by ultrasonication until individual nanosized droplets are formed. Dynamic light scattering and microscopic examination characterize the physical properties of the particles (particle size, charge and shape). Their biologic properties (cell uptake and retention, cytotoxicity and antiretroviral efficacy) are determined with human monocyte-derived macrophages (MDM). MDM are derived from human peripheral blood monocytes isolated from leukopacks using centrifugal elutriation for purification. Such blood-borne macrophages may be used as cellular transporters for nanoART distribution to human immunodeficiency virus (HIV) infected organs. We posit that the repackaging of clinically available antiretroviral medications into nanoparticles for HIV-1 treatments may improve compliance and positively affect disease outcomes. PMID:21178968

Inorganic arsenite alters macrophage generation from human peripheral blood monocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sakurai, Teruaki; Ohta, Takami; Fujiwara, Kitao

2005-03-01

Inorganic arsenite has caused severe inflammatory chronic poisoning in humans through the consumption of contaminated well water. In this study, we examined the effects of arsenite at nanomolar concentrations on the in vitro differentiation of human macrophages from peripheral blood monocytes. While arsenite was found to induce cell death in a culture system containing macrophage colony stimulating factor (M-CSF), macrophages induced by granulocyte-macrophage CSF (GM-CSF) survived the treatment, but were morphologically, phenotypically, and functionally altered. In particular, arsenite-induced cells expressed higher levels of a major histocompatibility complex (MHC) class II antigen, HLA-DR, and CD14. They were more effective at inducingmore » allogeneic or autologous T cell responses and responded more strongly to bacterial lipopolysaccharide (LPS) by inflammatory cytokine release as compared to cells induced by GM-CSF alone. On the other hand, arsenite-induced cells expressed lower levels of CD11b and CD54 and phagocytosed latex beads or zymosan particles less efficiently. We also demonstrated that the optimum amount of cellular reactive oxygen species (ROS) induced by nM arsenite might play an important role in this abnormal monocyte differentiation. This work may have implications in chronic arsenic poisoning because the total peripheral blood arsenic concentrations of these patients are at nM levels.« less

Eye Shape Using Partial Coherence Interferometry, Autorefraction and SD OCT

PubMed Central

Clark, Christopher A.; Elsner, Ann E.; Konynenbelt, Benjamin J.

2015-01-01

Purpose Peripheral refraction and retinal shape may influence refractive development. Peripheral refraction has been shown to have a high degree of variability and can take considerable time to perform. SD OCT and peripheral axial length measures may be more reliable, assuming that the retinal position is more important than the peripheral optics of the lens/cornea. Methods 79 subjects right eyes were imaged for this study (age range: 22 to 34 yr, refractive error: −10 to +5.00.) Thirty deg SD OCT (Spectralis, Heidleberg) images were collected in a radial pattern along with peripheral refraction with an autorefractor (Shin-Nippon Auto-refractor) and peripheral axial length measurements with partial coherence interferometry (PCI) (IOLmaster, Zeiss). Statistics were performed using repeat measures ANOVA in SPSS (IBM), Bland-Altman analyses, and regression. All measures were converted to diopters to allow direct comparison. Results SD OCT showed a retinal shape with an increased curvature for myopes compared to emmetropes/hyperopes. This retinal shape change became significant around 5 deg. The SD OCT analysis for retinal shape provides a resolution of 0.026 dipopters, which is about ten times more accurate than using autorefraction or clinical refractive techniques. Bland-Altman analyses suggest that retinal shape measured by SD OCT and the PCI method were more consistent with one another than either was with AR. Conclusions With more accurate measures of retinal shape using SD OCT, consistent differences between emmetrope/hyperopes and myopes were found nearer to the fovea than previously reported. Retinal shape may be influenced by central refractive error, and not merely peripheral optics. Partial coherence interferometry and SD OCT appear to be more accurate than autorefraction, which may be influenced other factors such as fixation and accommodation. Autorefraction does measure the optics directly, which may be a strength of that method. PMID:25437906

Derivation of Neural Stem Cells from Human Adult Peripheral CD34+ Cells for an Autologous Model of Neuroinflammation

PubMed Central

Wang, Tongguang; Choi, Elliot; Monaco, Maria Chiara G.; Campanac, Emilie; Medynets, Marie; Do, Thao; Rao, Prashant; Johnson, Kory R.; Elkahloun, Abdel G.; Von Geldern, Gloria; Johnson, Tory; Subramaniam, Sriram; Hoffman, Dax; Major, Eugene; Nath, Avindra

2013-01-01

Proinflammatory factors from activated T cells inhibit neurogenesis in adult animal brain and cultured human fetal neural stem cells (NSC). However, the role of inhibition of neurogenesis in human neuroinflammatory diseases is still uncertain because of the difficulty in obtaining adult NSC from patients. Recent developments in cell reprogramming suggest that NSC may be derived directly from adult fibroblasts. We generated NSC from adult human peripheral CD34+ cells by transfecting the cells with Sendai virus constructs containing Sox2, Oct3/4, c-Myc and Klf4. The derived NSC could be differentiated to glial cells and action potential firing neurons. Co-culturing NSC with activated autologous T cells or treatment with recombinant granzyme B caused inhibition of neurogenesis as indicated by decreased NSC proliferation and neuronal differentiation. Thus, we have established a unique autologous in vitro model to study the pathophysiology of neuroinflammatory diseases that has potential for usage in personalized medicine. PMID:24303066

Local blood flow in peripheral nerves and their ganglia: Resurrecting key ideas around its measurement and significance.

PubMed

Zochodne, Douglas W

2018-06-01

Over 3 decades ago, seminal work by Phillip Low and colleagues established exquisite physiology around the measurement of nerve blood flow (NBF). Although not widely explored recently, its connection to the clinic has awaited human methodology. While human studies have not achieved a convincing level of rigour, newer imaging technologies are offering early information. The peripheral nerve trunk has parallel blood flow compartments that include epineurial flow dominated by arteriovenous shunts and downstream endoneurial blood flow (EBF). NBF and EBF have lower values than central nervous system blood flow, lack autoregulation yet have sympathetic and peptidergic neurovascular control. Contrary to expectation, injury to nerves is often associated with rises in NBF rather than ischemia, a finding of biological interest corroborated by human studies. Despite its potential importance, quantitative human measurements of EBF and NBF are not yet available. However, with development, careful NBF analysis may present new insights into nerve disorders. Muscle Nerve 57: 884-895, 2018. © 2017 Wiley Periodicals, Inc.

The effects of stress on the enzymes of peripheral leukocytes

NASA Technical Reports Server (NTRS)

Leise, E. M.; Gray, I.

1973-01-01

Previous work showed an early response of rabbit and human leukocyte enzymes to the stress of bacterial infection. Since these represented a mixed population of leukocytes and since polymorphonuclear leukocytes (PMN) increased in these preparations, it was necessary to establish whether the observed increase in lactate dehydrenase (LDH) and protein was the result of an increase in any one particular cell type or in all cells. The need for the development of a simple reproducible method for the differential separation of peripheral leukocytes for the furtherance of our own studies was apparent. It was also becoming increasingly apparent that morphologically similar cells, such as small lymphocytes (L) and macrophages, were capable of different biological functions. A dextran gradient centrifugation method was developed which has provided an easily reproducible technique for separating L from PMN. During the course of this work, in which over 250 rabbits were examined, the pattern of daily leukocyte protein and enzyme variation became increasingly more apparent. This information could have some impact on future work with leukocyte enzymes, by our group and by other workers. The differences in normal protein and enzyme levels maintained by some individuals, and some inbred strains, were evaluated and reported separately. It has been shown that one type of leukocyte may react more to a given stress than other leukocytes.

Reflexology in the management of chemotherapy induced peripheral neuropathy: A pilot randomized controlled trial.

PubMed

Kurt, Seda; Can, Gulbeyaz

2018-02-01

The current experimental study aimed to evaluate the effectiveness of reflexology on the management of symptoms and functions of chemotherapy-induced peripheral neuropathy (CIPN) in cancer patients. This study was conducted as a randomized controlled trial in 60 patients (30 experimental and 30 control patients) who had chemotherapy-induced Grade II-IV peripheral neuropathy complaints from July 2013 to November 2015. Data were collected using the patient identification form, European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy (EORTC-CIPN-20) form, and BPI (used for related chemotherapy-induced peripheral neuropathy symptoms). The majority of the patients were being treated for gastrointestinal or breast cancer and were primarily receiving Eloxatine- or taxane-based treatment. It was found that reflexology applications did not lead to differences in either group in terms of peripheral neuropathy severity and incidence (p > 0.05) and only led to improvement in sensory functions in the experimental group (p < 0.05). It was determined that reflexology is not an effective method in the management of patients' activity levels, walking ability etc. and motor, autonomic functions related CIPN, but reflexology is effective method in the management of patients' sensory functions related CIPN. Key Words: Peripheral neuropathy, reflexology, chemotherapy, EORTC QLQ-CIPN-20, BPI. Copyright © 2017 Elsevier Ltd. All rights reserved.

Xenogeneic graft-versus-host-disease in NOD-scid IL-2Rγnull mice display a T-effector memory phenotype.

PubMed

Ali, Niwa; Flutter, Barry; Sanchez Rodriguez, Robert; Sharif-Paghaleh, Ehsan; Barber, Linda D; Lombardi, Giovanna; Nestle, Frank O

2012-01-01

The occurrence of Graft-versus-Host Disease (GvHD) is a prevalent and potentially lethal complication that develops following hematopoietic stem cell transplantation. Humanized mouse models of xenogeneic-GvHD based upon immunodeficient strains injected with human peripheral blood mononuclear cells (PBMC; "Hu-PBMC mice") are important tools to study human immune function in vivo. The recent introduction of targeted deletions at the interleukin-2 common gamma chain (IL-2Rγ(null)), notably the NOD-scid IL-2Rγ(null) (NSG) and BALB/c-Rag2(null) IL-2Rγ(null) (BRG) mice, has led to improved human cell engraftment. Despite their widespread use, a comprehensive characterisation of engraftment and GvHD development in the Hu-PBMC NSG and BRG models has never been performed in parallel. We compared engrafted human lymphocyte populations in the peripheral blood, spleens, lymph nodes and bone marrow of these mice. Kinetics of engraftment differed between the two strains, in particular a significantly faster expansion of the human CD45(+) compartment and higher engraftment levels of CD3(+) T-cells were observed in NSG mice, which may explain the faster rate of GvHD development in this model. The pathogenesis of human GvHD involves anti-host effector cell reactivity and cutaneous tissue infiltration. Despite this, the presence of T-cell subsets and tissue homing markers has only recently been characterised in the peripheral blood of patients and has never been properly defined in Hu-PBMC models of GvHD. Engrafted human cells in NSG mice shows a prevalence of tissue homing cells with a T-effector memory (T(EM)) phenotype and high levels of cutaneous lymphocyte antigen (CLA) expression. Characterization of Hu-PBMC mice provides a strong preclinical platform for the application of novel immunotherapies targeting T(EM)-cell driven GvHD.

Xenogeneic Graft-versus-Host-Disease in NOD-scid IL-2Rγnull Mice Display a T-Effector Memory Phenotype

PubMed Central

Ali, Niwa; Flutter, Barry; Sanchez Rodriguez, Robert; Sharif-Paghaleh, Ehsan; Barber, Linda D.; Lombardi, Giovanna; Nestle, Frank O.

2012-01-01

The occurrence of Graft-versus-Host Disease (GvHD) is a prevalent and potentially lethal complication that develops following hematopoietic stem cell transplantation. Humanized mouse models of xenogeneic-GvHD based upon immunodeficient strains injected with human peripheral blood mononuclear cells (PBMC; “Hu-PBMC mice”) are important tools to study human immune function in vivo. The recent introduction of targeted deletions at the interleukin-2 common gamma chain (IL-2Rγnull), notably the NOD-scid IL-2Rγnull (NSG) and BALB/c-Rag2 null IL-2Rγnull (BRG) mice, has led to improved human cell engraftment. Despite their widespread use, a comprehensive characterisation of engraftment and GvHD development in the Hu-PBMC NSG and BRG models has never been performed in parallel. We compared engrafted human lymphocyte populations in the peripheral blood, spleens, lymph nodes and bone marrow of these mice. Kinetics of engraftment differed between the two strains, in particular a significantly faster expansion of the human CD45+ compartment and higher engraftment levels of CD3+ T-cells were observed in NSG mice, which may explain the faster rate of GvHD development in this model. The pathogenesis of human GvHD involves anti-host effector cell reactivity and cutaneous tissue infiltration. Despite this, the presence of T-cell subsets and tissue homing markers has only recently been characterised in the peripheral blood of patients and has never been properly defined in Hu-PBMC models of GvHD. Engrafted human cells in NSG mice shows a prevalence of tissue homing cells with a T-effector memory (TEM) phenotype and high levels of cutaneous lymphocyte antigen (CLA) expression. Characterization of Hu-PBMC mice provides a strong preclinical platform for the application of novel immunotherapies targeting TEM-cell driven GvHD. PMID:22937164

Peripherally derived FGF21 promotes remyelination in the central nervous system

PubMed Central

Kuroda, Mariko; Maedera, Noriko; Koyama, Yoshihisa; Hamaguchi, Machika; Fujimura, Harutoshi; Konishi, Morichika; Itoh, Nobuyuki; Mochizuki, Hideki

2017-01-01

Demyelination in the central nervous system (CNS) leads to severe neurological deficits that can be partially reversed by spontaneous remyelination. Because the CNS is isolated from the peripheral milieu by the blood-brain barrier, remyelination is thought to be controlled by the CNS microenvironment. However, in this work we found that factors derived from peripheral tissue leak into the CNS after injury and promote remyelination in a murine model of toxin-induced demyelination. Mechanistically, leakage of circulating fibroblast growth factor 21 (FGF21), which is predominantly expressed by the pancreas, drives proliferation of oligodendrocyte precursor cells (OPCs) through interactions with β-klotho, an essential coreceptor of FGF21. We further confirmed that human OPCs expressed β-klotho and proliferated in response to FGF21 in vitro. Vascular barrier disruption is a common feature of many CNS disorders; thus, our findings reveal a potentially important role for the peripheral milieu in promoting CNS regeneration. PMID:28825598

Rheumatological manifestations in inflammatory bowel disease

PubMed Central

Voulgari, Paraskevi V.

2011-01-01

Rheumatological manifestations in inflammatory bowel disease (IBD) are frequent and include peripheral arthritis, axial involvement and peripheral enthesitis. Secondary osteoporosis and hypertrophic osteoarthropathy may also occur. Complications of IBD (e.g. septic arthritis) must be distinguished from sterile inflammation. Adverse effects of corticosteroid treatment, such as osteonecrosis, may also affect joints. Axial involvement ranges from low back pain to true ankylosing spondylitis. Human leukocyte antigen B27 is associated with axial involvement of IBD. Peripheral arthritis has been classified into two types. Type I is a pauciarticular, asymmetric usually non destructive arthritis affecting large joints and is usually associated with active bowel disease. Type II is a polyarthritis affecting small joints and tends to run a course independent of the bowel disease. Treatment of joint symptoms in IBD include sulphasalazine, azathioprine, methotrexate and glucocorticoids. Anti-tumor necrosis factor antibodies are effective in treating resistant or complicated Crohn’s disease as well as peripheral arthritis and axial involvement. PMID:24713717

Motor-commands decoding using peripheral nerve signals: a review

NASA Astrophysics Data System (ADS)

Hong, Keum-Shik; Aziz, Nida; Ghafoor, Usman

2018-06-01

During the last few decades, substantial scientific and technological efforts have been focused on the development of neuroprostheses. The major emphasis has been on techniques for connecting the human nervous system with a robotic prosthesis via natural-feeling interfaces. The peripheral nerves provide access to highly processed and segregated neural command signals from the brain that can in principle be used to determine user intent and control muscles. If these signals could be used, they might allow near-natural and intuitive control of prosthetic limbs with multiple degrees of freedom. This review summarizes the history of neuroprosthetic interfaces and their ability to record from and stimulate peripheral nerves. We also discuss the types of interfaces available and their applications, the kinds of peripheral nerve signals that are used, and the algorithms used to decode them. Finally, we explore the prospects for future development in this area.

PERIPHERAL PARASITAEMIA AND ITS ASSOCIATION WITH PLASMA CYTOKINES LEVELS IN MALARIA-INFECTED PREGNANT WOMEN IN ABA, ABIA STATE, NIGERIA.

PubMed

Ifeanyichukwu, M O; Okamgba, O C; Amilo, G I; Nwokorie, E A

2017-01-01

Cytokines in pregnant female may not be a normal phenomenon as malarial infection is often associated with strong CD4+ cell activation and up-regulation of pro-inflammatory cytokines. We investigated the relationship between peripheral parasitaemia and plasma levels of cytokines among malaria infected pregnant women in Aba, Abia State, Nigeria. A total of 206 non-HIV positive asymptomatic malaria parasitaemic (n=144) and non-parasitaemic (n=62) pregnant women were recruited for this study alongside 80 non-pregnant women who served as positive (n=40) and negative (n=40) controls. Blood samples were aseptically collected from each subject and tested for HIV and malaria parasites using standard methods. Also, plasma levels of cytokines were measured using Th1/Th2 human cytokine ELISA kits (Abcam, UK). Analysis of Variance and Student's t-test were used for Comparison of groups while Pearson's Correlation Coefficient was used for tests of association. The results revealed a mean parasite density of 685.56±484.55 parasites/µl of blood. Malaria infected pregnant subjects showed significantly higher levels of IFN-γ, TNF-α, IL-4, IL-6 and IL-10 when compared with their non-infected counterparts (P< 0.05). The cytokines evaluated were higher in moderate parasitaemia than mild parasitaemia. Positive correlation existed between peripheral parasite density (PPD) and IL-4 (r= 0.24, P=0.004), PPD and IL-6 (r = 0.35, P = 0.001) as well as PPD and IL-10 (r = 0.29, P = 0.001). This study showed that increase in peripheral parasitaemia increased levels of some plasma cytokines (IL-4, IL-6 and IL-10) but not IFN-γ and TNF-α in the malaria infected pregnant women studied.

Increased Protease-Activated Receptor-2 (PAR-2) Expression on CD14++CD16+ Peripheral Blood Monocytes of Patients with Severe Asthma

PubMed Central

Shrestha Palikhe, Nami; Nahirney, Drew; Laratta, Cheryl; Gandhi, Vivek Dipak; Vethanayagam, Dilini; Bhutani, Mohit; Mayers, Irvin

2015-01-01

Background Protease-Activated Receptor-2 (PAR-2), a G protein coupled receptor activated by serine proteases, is widely expressed in humans and is involved in inflammation. PAR-2 activation in the airways plays an important role in the development of allergic airway inflammation. PAR-2 expression is known to be upregulated in the epithelium of asthmatic subjects, but its expression on immune and inflammatory cells in patients with asthma has not been studied. Methods We recruited 12 severe and 24 mild/moderate asthmatics from the University of Alberta Hospital Asthma Clinics and collected baseline demographic information, medication use and parameters of asthma severity. PAR-2 expression on blood inflammatory cells was analyzed by flow cytometry. Results Subjects with severe asthma had higher PAR-2 expression on CD14++CD16+ monocytes (intermediate monocytes) and also higher percentage of CD14++CD16+PAR-2+ monocytes (intermediate monocytes expressing PAR-2) in blood compared to subjects with mild/moderate asthma. Receiver operating characteristics (ROC) curve analysis showed that the percent of CD14++CD16+PAR-2+ in peripheral blood was able to discriminate between patients with severe and those with mild/moderate asthma with high sensitivity and specificity. In addition, among the whole populations, subjects with a history of asthma exacerbations over the last year had higher percent of CD14++CD16+ PAR-2+ cells in peripheral blood compared to subjects without exacerbations. Conclusions PAR-2 expression is increased on CD14++CD16+ monocytes in the peripheral blood of subjects with severe asthma and may be a biomarker of asthma severity. Our data suggest that PAR-2 -mediated activation of CD14++CD16+ monocytes may play a role in the pathogenesis of severe asthma. PMID:26658828

Measurement of surface roughness changes of unpolished and polished enamel following erosion

PubMed Central

Austin, Rupert S.; Parkinson, Charles R.; Hasan, Adam; Bartlett, David W.

2017-01-01

Objectives To determine if Sa roughness data from measuring one central location of unpolished and polished enamel were representative of the overall surfaces before and after erosion. Methods Twenty human enamel sections (4x4 mm) were embedded in bis-acryl composite and randomised to either a native or polishing enamel preparation protocol. Enamel samples were subjected to an acid challenge (15 minutes 100 mL orange juice, pH 3.2, titratable acidity 41.3mmol OH/L, 62.5 rpm agitation, repeated for three cycles). Median (IQR) surface roughness [Sa] was measured at baseline and after erosion from both a centralised cluster and four peripheral clusters. Within each cluster, five smaller areas (0.04 mm2) provided the Sa roughness data. Results For both unpolished and polished enamel samples there were no significant differences between measuring one central cluster or four peripheral clusters, before and after erosion. For unpolished enamel the single central cluster had a median (IQR) Sa roughness of 1.45 (2.58) μm and the four peripheral clusters had a median (IQR) of 1.32 (4.86) μm before erosion; after erosion there were statistically significant reductions to 0.38 (0.35) μm and 0.34 (0.49) μm respectively (p<0.0001). Polished enamel had a median (IQR) Sa roughness 0.04 (0.17) μm for the single central cluster and 0.05 (0.15) μm for the four peripheral clusters which statistically significantly increased after erosion to 0.27 (0.08) μm for both (p<0.0001). Conclusion Measuring one central cluster of unpolished and polished enamel was representative of the overall enamel surface roughness, before and after erosion. PMID:28771562

Peripherally cross-linking the shell of core-shell polymer micelles decreases premature release of physically loaded combretastatin A4 in whole blood and increases its mean residence time and subsequent potency against primary murine breast tumors after IV administration.

PubMed

Wakaskar, Rajesh R; Bathena, Sai Praneeth R; Tallapaka, Shailendra B; Ambardekar, Vishakha V; Gautam, Nagsen; Thakare, Rhishikesh; Simet, Samantha M; Curran, Stephen M; Singh, Rakesh K; Dong, Yuxiang; Vetro, Joseph A

2015-03-01

Determine the feasibility and potential benefit of peripherally cross-linking the shell of core-shell polymer micelles on the premature release of physically loaded hydrophobic drug in whole blood and subsequent potency against solid tumors. Individual Pluronic F127 polymer micelles (F127 PM) peripherally cross-linked with ethylenediamine at 76% of total PEO blocks (X-F127 PM) were physically loaded with combretastatin A4 (CA4) by the solid dispersion method and compared to CA4 physically loaded in uncross-linked F127 PM, CA4 in DMSO in vitro, or water-soluble CA4 phosphate (CA4P) in vivo. X-F127 PM had similar CA4 loading and aqueous solubility as F127 PM up to 10 mg CA4 / mL at 22.9 wt% and did not aggregate in PBS or 90% (v/v) human serum at 37°C for at least 24 h. In contrast, X-F127 PM decreased the unbound fraction of CA4 in whole blood (fu) and increased the mean plasma residence time and subsequent potency of CA4 against the vascular function and growth of primary murine 4T1 breast tumors over CA4 in F127 PM and water-soluble CA4P after IV administration. Given that decreasing the fu is an indication of decreased drug release, peripherally cross-linking the shell of core-shell polymer micelles may be a simple approach to decrease premature release of physically loaded hydrophobic drug in the blood and increase subsequent potency in solid tumors.

Peripheral Vision Can Influence Eye Growth and Refractive Development in Infant Monkeys

PubMed Central

Smith, Earl L.; Kee, Chea-su; Ramamirtham, Ramkumar; Qiao-Grider, Ying; Hung, Li-Fang

2006-01-01

PURPOSE Given the prominence of central vision in humans, it has been assumed that visual signals from the fovea dominate emmetropization. The purpose of this study was to examine the impact of peripheral vision on emmetropization. METHODS Bilateral, peripheral form deprivation was produced in 12 infant monkeys by rearing them with diffusers that had either 4- or 8-mm apertures centered on the pupils of each eye, to allow 24° or 37° of unrestricted central vision, respectively. At the end of the lens-rearing period, an argon laser was used to ablate the fovea in one eye of each of seven monkeys. Subsequently, all the animals were allowed unrestricted vision. Refractive error and axial dimensions were measured along the pupillary axis by retinoscopy and A-scan ultrasonography, respectively. Control data were obtained from 21 normal monkeys and 3 infants reared with binocular plano lenses. RESULTS Nine of the 12 treated monkeys had refractive errors that fell outside the 10th- and 90th-percentile limits for the age-matched control subjects, and the average refractive error for the treated animals was more variable and significantly less hyperopic/more myopic (+0.03 ± 2.39 D vs. +2.39 ± 0.92 D). The refractive changes were symmetric in the two eyes of a given animal and axial in nature. After lens removal, all the treated monkeys recovered from the induced refractive errors. No interocular differences in the recovery process were observed in the animals with monocular foveal lesions. CONCLUSIONS On the one hand, the peripheral retina can contribute to emmetropizing responses and to ametropias produced by an abnormal visual experience. On the other hand, unrestricted central vision is not sufficient to ensure normal refractive development, and the fovea is not essential for emmetropizing responses. PMID:16249469

Measurement of an Elasticity Map in the Human Cornea

PubMed Central

Mikula, Eric R.; Jester, James V.; Juhasz, Tibor

2016-01-01

Purpose The biomechanical properties of the cornea have an important role in determining the shape of the cornea and visual acuity. Since the cornea is a nonhomogeneous tissue, it is thought that the elastic properties vary throughout the cornea. We aim to measure a map of corneal elasticity across the cornea. Methods An acoustic radiation force elasticity microscope (ARFEM) was used to create a map of corneal elasticity in the human cornea. This ARFEM uses a low frequency, high intensity acoustic force to displace a femtosecond laser-generated microbubble, while using a high frequency, low intensity ultrasound to monitor the position of the microbubble within the cornea. From the displacement of the bubble and the magnitude of the acoustic radiation force, the local value of corneal elasticity is calculated in the direction of the displacement. Measurements were conducted at 6 locations, ranging from the central to peripheral cornea at anterior and posterior depths. Results The mean anterior elastic moduli were 4.2 ± 1.2, 3.4 ± 0.7, and 1.9 ± 0.7 kPa in the central, mid, and peripheral regions, respectively, while the posterior elastic moduli were 2.3 ± 0.7, 1.6 ± 0.3, and 2.9 ± 1.2 kPa in the same radial locations. Conclusions We found that there is a unique distribution of elasticity axially and radially throughout the cornea. PMID:27327584

Increased Numbers of CD4+CD25+ and CD8+CD25+ T-Cells in Peripheral Blood of Patients with Rheumatoid Arthritis with Parvovirus B19 Infection

PubMed Central

NACIUTE, MILDA; MACIUNAITE, GABRIELE; MIELIAUSKAITE, DIANA; RUGIENE, RITA; ZINKEVICIENE, AUKSE; MAURICAS, MYKOLAS; MUROVSKA, MODRA; GIRKONTAITE, IRUTE

2017-01-01

Aim: To investigate T-cell subpopulations in peripheral blood of human parvovirus B19 DNA-positive (B19+) and -negative (B19−) patients with rheumatoid arthritis (RA) and healthy persons. Patients and Methods: Blood samples were collected from 115 patients with RA and 47 healthy volunteers; 27 patients with RA and nine controls were B19+. Cluster of differentiation (CD) 4, 8, 25 and 45RA were analyzed on blood cells. CD25 expression on CD4+CD45RA+, CD4+CD45RA−, CD8+CD45RA+, CD8+CD45RA− subsets were analyzed by flow cytometry. Results: The percentage of CD25low and CD25hi cells was increased on CD4+CD45RA+, CD4+CD45RA− T-cells and the percentage of CD25+ cells was increased on CD8+CD45RA+, CD8+CD45RA− T-cells of B19+ patients with RA in comparison with B19− patients and controls. Conclusion: Raised levels of CD4 and CD8 regulatory T-cells in B19+ RA patients could cause down-regulation of antiviral clearance mechanisms and lead to activation of persistent human parvovirus B19 infection in patients with RA PMID:28358698

Generation of human anti-MUC3 IgG antibodies after in vitro immunization of naive peripheral blood B-lymphocytes.

PubMed

Baritaki, S; Zafiropoulos, A; Georgopoulos, E; Souris, S; Krambovitis, E

2001-04-01

It has been demonstrated that IgG antibodies can be generated to self-antigen peptides as well as against viral antigens by an antigen-specific in vitro immunization system of resting human peripheral B-lymphocytes. Using a synthetic peptide from the consensus variable tandem-repeat region of the MUC3 mucin (TSSITTTGTTSHSTPSP) as the B cell epitope, we immunized blood donor B-lymphocytes in vitro and tested for MUC3-specific antibodies by ELISA. After the primary activation step all antibodies were IgM. At the end of the secondary immunization step we obtained 1.8% (21/1138) of the cultures with IgG-switched antibodies. In a competitive inhibition ELISA using the MUC1, MUC2, MUC3, MUC4 and PIP2 peptides, only one culture (F8.1) gave satisfactory specific inhibition. Using this antibody in fluorometric studies, it stained cells from two colon carcinoma cell lines predominantly in the cytoplasm, whereas those from a breast cancer cell line stained predominantly the cell surface. In a preliminary immunohistological evaluation with formalin-fixed sections, the antibody appeared to moderately stain colon sections, but not breast sections or lymph node. This method of in vitro immunization may be a useful tool in generating IgG antibodies specific to self-antigens and could find applications in tumour targeting and immunotherapy.

Ontogeny of anti-human immunodeficiency virus (HIV) antibody production in HIV-1-infected infants.

PubMed Central

Pollack, H; Zhan, M X; Ilmet-Moore, T; Ajuang-Simbiri, K; Krasinski, K; Borkowsky, W

1993-01-01

The early serologic response of infants to infection with human immunodeficiency virus type 1 (HIV-1) is normally obscured by the presence of transplacentally acquired maternal HIV antibody. By measuring HIV antibody produced in vitro by lymphocytes isolated from peripheral blood of infants and children of HIV-1-infected mothers, we have been able to study the natural acquisition of humoral immunity to perinatal HIV-1 infection. One hundred ninety-seven infants of HIV-1-infected women were studied prospectively and longitudinally from birth. In the neonatal period, infected infants produced only small amounts of HIV-specific IgG antibodies to a restricted number of antigens. The amount of immunoglobulin to HIV-1 and the number of HIV-1 antigens recognized increased with age. After 6 months of life 85% of infected infants made detectable antibody to two or more viral proteins. Antibody to gp160 appeared first and was the most frequently found at all ages, followed by antibody to the envelope proteins gp120 and gp41. The amount of HIV antibody produced correlated positively with the percentage of CD4+ T lymphocytes in peripheral blood. This assay provides a method of studying the immunogenicity of vaccines against HIV-1 in HIV-1-infected infants and of assessing the effect of early therapeutic interventions on the humoral response to HIV-1. PMID:8460144

Cryopreserved Human Allografts for the Reconstruction of Aortic and Peripheral Prosthetic Graft Infection.

PubMed

Bossi, Matteo; Tozzi, Matteo; Franchin, Marco; Ferraro, Stefania; Rivolta, Nicola; Ferrario, Massimo; Guttadauro, Chiara; Castelli, Patrizio; Piffaretti, Gabriele

2017-12-25

Background : This study aimed to present cases with cryopreserved human allografts (CHAs) for vascular reconstruction in both aortic and peripheral infected prosthetic grafts. Materials and Methods : This is a single center, observational descriptive study with retrospective analysis. In all cases, the infected prosthetic graft material was completely removed. At discharge, patients were administered anticoagulants. Follow-up examinations included clinical visits, echo-color-Doppler ultrasounds, or computed tomography angiography within 30 days and at 3, 6, and 12 months after the treatment, and then twice per year. Results : We treated 21 patients (90% men, n=19) with the mean age of 71±12 years and mean interval between the initial operation and replacement with CHA of 30 months [range, 1-216; interquartile range (IQR), 2-36]. In-hospital mortality was 14% (n=3); no CHA-related complication led to death. Limb salvage was 100%. No patient was lost at the median follow-up of 14 months (range, 2-61; IQR, 6-39). No rupture, aneurysmal degeneration, or re-infection occurred. Estimated freedom from CHA-related adverse events (95% confidence interval, 43-63) was 95% at 3 years. Conclusion : In our experience, CHAs are a viable option for prosthetic graft infections and provide satisfactory clinical results and favorable stability because of a very low rate of CHA-related adverse events during follow-up.

Recognition of Handwriting from Electromyography

PubMed Central

Linderman, Michael; Lebedev, Mikhail A.; Erlichman, Joseph S.

2009-01-01

Handwriting – one of the most important developments in human culture – is also a methodological tool in several scientific disciplines, most importantly handwriting recognition methods, graphology and medical diagnostics. Previous studies have relied largely on the analyses of handwritten traces or kinematic analysis of handwriting; whereas electromyographic (EMG) signals associated with handwriting have received little attention. Here we show for the first time, a method in which EMG signals generated by hand and forearm muscles during handwriting activity are reliably translated into both algorithm-generated handwriting traces and font characters using decoding algorithms. Our results demonstrate the feasibility of recreating handwriting solely from EMG signals – the finding that can be utilized in computer peripherals and myoelectric prosthetic devices. Moreover, this approach may provide a rapid and sensitive method for diagnosing a variety of neurogenerative diseases before other symptoms become clear. PMID:19707562

Frequency and genetic characterization of V(DD)J recombinants in the human peripheral blood antibody repertoire.

PubMed

Briney, Bryan S; Willis, Jordan R; Hicar, Mark D; Thomas, James W; Crowe, James E

2012-09-01

Antibody heavy-chain recombination that results in the incorporation of multiple diversity (D) genes, although uncommon, contributes substantially to the diversity of the human antibody repertoire. Such recombination allows the generation of heavy chain complementarity determining region 3 (HCDR3) regions of extreme length and enables junctional regions that, because of the nucleotide bias of N-addition regions, are difficult to produce through normal V(D)J recombination. Although this non-classical recombination process has been observed infrequently, comprehensive analysis of the frequency and genetic characteristics of such events in the human peripheral blood antibody repertoire has not been possible because of the rarity of such recombinants and the limitations of traditional sequencing technologies. Here, through the use of high-throughput sequencing of the normal human peripheral blood antibody repertoire, we analysed the frequency and genetic characteristics of V(DD)J recombinants. We found that these recombinations were present in approximately 1 in 800 circulating B cells, and that the frequency was severely reduced in memory cell subsets. We also found that V(DD)J recombination can occur across the spectrum of diversity genes, indicating that virtually all recombination signal sequences that flank diversity genes are amenable to V(DD)J recombination. Finally, we observed a repertoire bias in the diversity gene repertoire at the upstream (5') position, and discovered that this bias was primarily attributable to the order of diversity genes in the genomic locus. © 2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd.

Polysaccharopeptides derived from Coriolus versicolor potentiate the S-phase specific cytotoxicity of Camptothecin (CPT) on human leukemia HL-60 cells

PubMed Central

2010-01-01

Background Polysaccharopeptide (PSP) from Coriolus versicolor (Yunzhi) is used as a supplementary cancer treatment in Asia. The present study aims to investigate whether PSP pre-treatment can increase the response of the human leukemia HL-60 cells to apoptosis induction by Camptothecin (CPT). Methods We used bivariate bromodeoxyuridine/propidium iodide (BrdUrd/PI) flow cytometry analysis to measure the relative movement (RM) of the BrdUrd positively labeled cells and DNA synthesis time (Ts) on the HL-60 cell line. We used annexin V/PI flow cytometry analysis to quantify the viable, necrotic and apoptotic cells. The expression of cyclin E and cyclin B1 was determined with annexin V/PI flow cytometry and western blotting. Human peripheral blood mononuclear cells were used to test the cytotoxicity of PSP and CPT. Results PSP reduced cellular proliferation; inhibited cells progression through both S and G2 phase, reduced 3H-thymidine uptake and prolonged DNA synthesis time (Ts) in HL-60 cells. PSP-pretreated cells enhanced the cytotoxicity of CPT. The sensitivity of cells to the cytotoxic effects of CPT was seen to be the highest in the S-phase and to a small extent of the G2 phase of the cell cycle. On the other hand, no cell death (measured by annexin V/PI) was evident with the normal human peripheral blood mononuclear cells with treatment of either PSP or CPT. Conclusion The present study shows that PSP increases the sensitization of the HL-60 cells to undergo effective apoptotic cell death induced by CPT. The pattern of sensitivity of cancer cells is similar to that of HL-60 cells. PSP rapidly arrests and/or kills cells in S-phase and did not interfere with the anticancer action of CPT. PSP is a potential adjuvant to treat human leukemia as rapidly proliferating tumors is characterized by a high proportion of S-phase cells. PMID:20423495

Endotoxin-associated protein: a potent stimulus for human granulocytopoietic activity which may be accessory cell independent.

PubMed Central

Bjornson, B H; Agura, E; Harvey, J M; Johns, M; Andrews, R G; McCabe, W R

1988-01-01

Proteins coextracted with endotoxin, termed endotoxin-associated protein (EAP), have been shown to exert interleukin 1-like activities. The present studies demonstrate that EAP also exerts potent granulopoietic colony-stimulating activity (CSA) on human peripheral blood and bone marrow progenitor cells, comparable to that seen with various types of conditioned media. The CSA observed with EAP appeared to be heat (100 degrees C, 30 min) and trypsin resistant and partially pronase resistant. Similar resistance was observed with the porin proteins of the outer membrane of gram-negative bacteria, and similar CSA activity was observed with a purified porin preparation of Neisseria gonorrhoeae. The CSA of EAP could be demonstrated in human peripheral blood and bone marrow leukocytes rigorously depleted of monocytes, T lymphocytes, and B lymphocytes by treatment with specific monoclonal antibodies and complement. PMID:2836311

Evidence for specific annexin I-binding proteins on human monocytes.

PubMed Central

Goulding, N J; Pan, L; Wardwell, K; Guyre, V C; Guyre, P M

1996-01-01

Recombinant human annexin I and a monoclonal antibody specific for this protein (mAb 1B) were used to investigate surface binding of this member of the annexin family of proteins to peripheral blood monocytes. Flow cytometric analysis demonstrated trypsin-sensitive, saturable binding of annexin I to human peripheral blood monocytes but not to admixed lymphocytes. A monoclonal antibody that blocks the anti-phospholipase activity of annexin I also blocked its binding to monocytes. These findings suggest the presence of specific binding sites on monocytes. Furthermore, surface iodination, immunoprecipitation and SDS/PAGE analysis were used to identify two annexin I-binding proteins on the surface of monocytes with molecular masses of 15 kDa and 18 kDa respectively. The identification and characterization of these annexin I-binding molecules should help us to better understand the specific interactions of annexin I with monocytes that lead to down-regulation of pro-inflammatory cell functions. PMID:8687405

Gene Expression Signatures Diagnose Influenza and Other Symptomatic Respiratory Viral Infection in Humans

PubMed Central

Zaas, Aimee K.; Chen, Minhua; Varkey, Jay; Veldman, Timothy; Hero, Alfred O.; Lucas, Joseph; Huang, Yongsheng; Turner, Ronald; Gilbert, Anthony; Lambkin-Williams, Robert; Øien, N. Christine; Nicholson, Bradly; Kingsmore, Stephen; Carin, Lawrence; Woods, Christopher W.; Ginsburg, Geoffrey S.

2010-01-01

Summary Acute respiratory infections (ARI) are a common reason for seeking medical attention and the threat of pandemic influenza will likely add to these numbers. Using human viral challenge studies with live rhinovirus, respiratory syncytial virus, and influenza A, we developed peripheral blood gene expression signatures that distinguish individuals with symptomatic ARI from uninfected individuals with > 95% accuracy. We validated this “acute respiratory viral” signature - encompassing genes with a known role in host defense against viral infections - across each viral challenge. We also validated the signature in an independently acquired dataset for influenza A and classified infected individuals from healthy controls with 100% accuracy. In the same dataset, we could also distinguish viral from bacterial ARIs (93% accuracy). These results demonstrate that ARIs induce changes in human peripheral blood gene expression that can be used to diagnose a viral etiology of respiratory infection and triage symptomatic individuals. PMID:19664979

The Place of Nailfold Capillaroscopy Among Instrumental Methods for Assessment of Some Peripheral Ischaemic Syndromes in Rheumatology.

PubMed

Lambova, Sevdalina N

2016-01-01

Micro- and macrovascular pathology is a frequent finding in a number of common rheumatic diseases. Secondary Raynaud's phenomenon (RP) is among the most common symptoms in systemic sclerosis and several other systemic autoimmune diseases including a broad differential diagnosis. It should be also differential from other peripheral vascular syndromes such as embolism, thrombosis, etc., some of which lead to clinical manifestation of the blue toe syndrome. The current review discusses the instrumental methods for vascular assessments. Nailfold capillaroscopy is the only method among the imaging techniques that can be used for morphological assessment of the nutritive capillaries in the nailfold area. Laser-Doppler flowmetry and laser-Doppler imaging are methods for functional assessment of microcirculation, while thermography and plethysmography reflect both blood flow in peripheral arteries and microcirculation. Doppler ultrasound and angiography visualize peripheral arteries. The choice of the appropriate instrumental method is guided by the clinical presentation. The main role of capillaroscopy is to provide differential diagnosis between primary and secondary RP. In rheumatology, capillaroscopic changes in systemic sclerosis have been recently defined as diagnostic. The appearance of abnormal capillaroscopic pattern inherits high positive predictive value for the development of a connective tissue disease that is higher than the predictive value of antinuclear antibodies. In cases of abrupt onset of peripheral ischaemia, clinical signs of critical ischaemia, unilateral or lower limb involvement, Doppler ultrasound and angiography are indicated. The most common causes for such clinical picture that may be referred to rheumatologic consultation are the antiphospholipid syndrome, mimickers of vasculitides such as atherosclerosis with cholesterol emboli, and neoplasms.

Metabolic Interactions of Purine Derivatives with Human ABC Transporter ABCG2: Genetic Testing to Assess Gout Risk.

PubMed

Ishikawa, Toshihisa; Aw, Wanping; Kaneko, Kiyoko

2013-11-04

In mammals, excess purine nucleosides are removed from the body by breakdown in the liver and excretion from the kidneys. Uric acid is the end product of purine metabolism in humans. Two-thirds of uric acid in the human body is normally excreted through the kidney, whereas one-third undergoes uricolysis (decomposition of uric acid) in the gut. Elevated serum uric acid levels result in gout and could be a risk factor for cardiovascular disease and diabetes. Recent studies have shown that human ATP-binding cassette transporter ABCG2 plays a role of renal excretion of uric acid. Two non-synonymous single nucleotide polymorphisms (SNPs), i.e., 421C>A (major) and 376C>T (minor), in the ABCG2 gene result in impaired transport activity, owing to ubiquitination-mediated proteosomal degradation and truncation of ABCG2, respectively. These genetic polymorphisms are associated with hyperuricemia and gout. Allele frequencies of those SNPs are significantly higher in Asian populations than they are in African and Caucasian populations. A rapid and isothermal genotyping method has been developed to detect the SNP 421C>A, where one drop of peripheral blood is sufficient for the detection. Development of simple genotyping methods would serve to improve prevention and early therapeutic intervention for high-risk individuals in personalized healthcare.

The peripheral clock regulates human pigmentation.

PubMed

Hardman, Jonathan A; Tobin, Desmond J; Haslam, Iain S; Farjo, Nilofer; Farjo, Bessam; Al-Nuaimi, Yusur; Grimaldi, Benedetto; Paus, Ralf

2015-04-01

Although the regulation of pigmentation is well characterized, it remains unclear whether cell-autonomous controls regulate the cyclic on-off switching of pigmentation in the hair follicle (HF). As human HFs and epidermal melanocytes express clock genes and proteins, and given that core clock genes (PER1, BMAL1) modulate human HF cycling, we investigated whether peripheral clock activity influences human HF pigmentation. We found that silencing BMAL1 or PER1 in human HFs increased HF melanin content. Furthermore, tyrosinase expression and activity, as well as TYRP1 and TYRP2 mRNA levels, gp100 protein expression, melanocyte dendricity, and the number gp100+ HF melanocytes, were all significantly increased in BMAL1 and/or PER1-silenced HFs. BMAL1 or PER1 silencing also increased epidermal melanin content, gp100 protein expression, and tyrosinase activity in human skin. These effects reflect direct modulation of melanocytes, as BMAL1 and/or PER1 silencing in isolated melanocytes increased tyrosinase activity and TYRP1/2 expression. Mechanistically, BMAL1 knockdown reduces PER1 transcription, and PER1 silencing induces phosphorylation of the master regulator of melanogenesis, microphthalmia-associated transcription factor, thus stimulating human melanogenesis and melanocyte activity in situ and in vitro. Therefore, the molecular clock operates as a cell-autonomous modulator of human pigmentation and may be targeted for future therapeutic strategies.

Pig but not Human Interferon-γ Initiates Human Cell-Mediated Rejection of Pig Tissue in vivo

NASA Astrophysics Data System (ADS)

Sultan, Parvez; Murray, Allan G.; McNiff, Jennifer M.; Lorber, Marc I.; Askenase, Philip W.; Bothwell, Alfred L. M.; Pober, Jordan S.

1997-08-01

Split-thickness pig skin was transplanted on severe combined immunodeficient mice so that pig dermal microvessels spontaneously inosculated with mouse microvessels and functioned to perfuse the grafts. Pig endothelial cells in the healed grafts constitutively expressed class I and class II major histocompatibility complex molecules. Major histocompatibility complex molecule expression could be further increased by intradermal injection of pig interferon-γ (IFN-γ ) but not human IFN-γ or tumor necrosis factor. Grafts injected with pig IFN-γ also developed a sparse infiltrate of mouse neutrophils and eosinophils without evidence of injury. Introduction of human peripheral blood mononuclear cells into the animals by intraperitoneal inoculation resulted in sparse perivascular mononuclear cell infiltrates in the grafts confined to the pig dermis. Injection of pig skin grafts on mice that received human peripheral blood mononuclear cells with pig IFN-γ (but not human IFN-γ or heat-inactivated pig IFN-γ ) induced human CD4+ and CD8+ T cells and macrophages to more extensively infiltrate the pig skin grafts and injure pig dermal microvessels. These findings suggest that human T cell-mediated rejection of xenotransplanted pig organs may be prevented if cellular sources of pig interferon (e.g., passenger lymphocytes) are eliminated from the graft.

Analysis of peripheral B cells and autoantibodies against the anti-nicotinic acetylcholine receptor derived from patients with myasthenia gravis using single-cell manipulation tools

PubMed Central

Terakawa, Maki; Muneoka, Satoshi; Nagahira, Kazuhiro; Nagane, Yuriko; Yamate, Jyoji; Motomura, Masakatsu; Utsugisawa, Kimiaki

2017-01-01

The majority of patients with myasthenia gravis (MG), an organ-specific autoimmune disease, harbor autoantibodies that attack the nicotinic acetylcholine receptor (nAChR-Abs) at the neuromuscular junction of skeletal muscles, resulting in muscle weakness. Single cell manipulation technologies coupled with genetic engineering are very powerful tools to examine T cell and B cell repertoires and the dynamics of adaptive immunity. These tools have been utilized to develop mAbs in parallel with hybridomas, phage display technologies and B-cell immortalization. By applying a single cell technology and novel high-throughput cell-based binding assays, we identified peripheral B cells that produce pathogenic nAChR-Abs in patients with MG. Although anti-nAChR antibodies produced by individual peripheral B cells generally exhibited low binding affinity for the α-subunit of the nAChR and great sequence diversity, a small fraction of these antibodies bound with high affinity to native-structured nAChRs on cell surfaces. B12L, one such Ab isolated here, competed with a rat Ab (mAb35) for binding to the human nAChR and thus considered to recognize the main immunogenic region (MIR). By evaluating the Ab in in vitro cell-based assays and an in vivo rat passive transfer model, B12L was found to act as a pathogenic Ab in rodents and presumably in humans.These findings suggest that B cells in peripheral blood may impact MG pathogenicity. Our methodology can be applied not only to validate pathogenic Abs as molecular target of MG treatment, but also to discover and analyze Ab production systems in other human diseases. PMID:29040265

Analysis of peripheral B cells and autoantibodies against the anti-nicotinic acetylcholine receptor derived from patients with myasthenia gravis using single-cell manipulation tools.

PubMed

Makino, Tomohiro; Nakamura, Ryuichi; Terakawa, Maki; Muneoka, Satoshi; Nagahira, Kazuhiro; Nagane, Yuriko; Yamate, Jyoji; Motomura, Masakatsu; Utsugisawa, Kimiaki

2017-01-01

The majority of patients with myasthenia gravis (MG), an organ-specific autoimmune disease, harbor autoantibodies that attack the nicotinic acetylcholine receptor (nAChR-Abs) at the neuromuscular junction of skeletal muscles, resulting in muscle weakness. Single cell manipulation technologies coupled with genetic engineering are very powerful tools to examine T cell and B cell repertoires and the dynamics of adaptive immunity. These tools have been utilized to develop mAbs in parallel with hybridomas, phage display technologies and B-cell immortalization. By applying a single cell technology and novel high-throughput cell-based binding assays, we identified peripheral B cells that produce pathogenic nAChR-Abs in patients with MG. Although anti-nAChR antibodies produced by individual peripheral B cells generally exhibited low binding affinity for the α-subunit of the nAChR and great sequence diversity, a small fraction of these antibodies bound with high affinity to native-structured nAChRs on cell surfaces. B12L, one such Ab isolated here, competed with a rat Ab (mAb35) for binding to the human nAChR and thus considered to recognize the main immunogenic region (MIR). By evaluating the Ab in in vitro cell-based assays and an in vivo rat passive transfer model, B12L was found to act as a pathogenic Ab in rodents and presumably in humans.These findings suggest that B cells in peripheral blood may impact MG pathogenicity. Our methodology can be applied not only to validate pathogenic Abs as molecular target of MG treatment, but also to discover and analyze Ab production systems in other human diseases.

Endurance exercise training increases peripheral vascular response in human fingers.

PubMed

Katayama, K; Shimoda, M; Maeda, J; Takemiya, T

1998-10-01

The purpose of this study was to clarify whether peripheral vascular response to alteration of transmural pressure is changed by endurance exercise training. The healthy male subjects (training group; n = 6) performed endurance exercise training that consisted of cycle ergometer exercise 5 d.week-1 and 30 min.d-1 for a period of 8 weeks. Changes in the peripheral vascular response to alteration of transmural pressure in the human finger were measured by a differential digital photoplethysmogram (DeltaDPG) and blood pressure during passive movement of the arm to different vertical hand positions relative to heart level. Following 8 weeks of endurance training, percent changes in DeltaDPG from heart level in the training group increased significantly (mean +/- SD, -48.1 +/- 7. 3 to -58.7 +/- 9.3% at the lowered position, 46.1 +/- 13.4 to 84.6 +/- 8.8% at the elevated position, p<0.05). Similarly, the arterial compliance index, which was calculated from DeltaDPG-P wave amplitude and arterial pulse pressure, also significantly changed in the training group over the 8 weeks (5.6 +/- 1.3 to 2.7 +/- 1.6 mV. V-1.s-1.mmHg-1 at the lowered position, 30.0 +/- 12.4 to 54.4 +/- 18. 9 mV.V-1.s-1.mmHg-1 at the elevated position ). Maximal oxygen uptake (V.O2 max) was significantly increased in the training group. On the other hand, the control group (n = 6) showed no significant changes in all parameters for 8 weeks. Therefore these results suggest that endurance exercise training induces an increase in peripheral vascular response to alteration of transmural pressure in the human finger.

Cocoa Consumption Alters the Global DNA Methylation of Peripheral Leukocytes in Humans with Cardiovascular Disease Risk Factors: A Randomized Controlled Trial

PubMed Central

Crescenti, Anna; Solà, Rosa; Valls, Rosa M.; Caimari, Antoni; del Bas, Josep M.; Anguera, Anna; Anglés, Neus; Arola, Lluís

2013-01-01

DNA methylation regulates gene expression and can be modified by different bioactive compounds in foods, such as polyphenols. Cocoa is a rich source of polyphenols, but its role in DNA methylation is still unknown. The objective was to assess the effect of cocoa consumption on DNA methylation and to determine whether the enzymes involved in the DNA methylation process participate in the mechanisms by which cocoa exerts these effects in humans. The global DNA methylation levels in the peripheral blood were evaluated in 214 volunteers who were pre-hypertensive, stage-1 hypertensive or hypercholesterolemic. The volunteers were divided into two groups: 110 subjects who consumed cocoa (6 g/d) for two weeks and 104 control subjects. In addition, the peripheral blood mononuclear cells (PBMCs) from six subjects were treated with a cocoa extract to analyze the mRNA levels of the DNA methyltransferases (DNMTs), methylenetetrahydrofolate reductase (MTHFR), and methionine synthase reductase (MTRR) genes. Cocoa consumption significantly reduced the DNA methylation levels (2.991±0.366 vs. 3.909±0.380, p<0.001). Additionally, we found an association between the cocoa effects on DNA methylation and three polymorphisms located in the MTHFR, MTRR, and DNMT3B genes. Furthermore, in PBMCs, the cocoa extract significantly lowered the mRNA levels of the DNMTs, MTHFR, and MTRR. Our study demonstrates for the first time that the consumption of cocoa decreases the global DNA methylation of peripheral leukocytes in humans with cardiovascular risk factors. In vitro experiments with PBMCs suggest that cocoa may exert this effect partially via the down-regulation of DNMTs, MTHFR and MTRR, which are key genes involved in this epigenetic process. Trial Registration Clinicaltrials.gov NCT00511420 and NCT00502047 PMID:23840361

Cocoa Consumption Alters the Global DNA Methylation of Peripheral Leukocytes in Humans with Cardiovascular Disease Risk Factors: A Randomized Controlled Trial.

PubMed

Crescenti, Anna; Solà, Rosa; Valls, Rosa M; Caimari, Antoni; Del Bas, Josep M; Anguera, Anna; Anglés, Neus; Arola, Lluís

2013-01-01

DNA methylation regulates gene expression and can be modified by different bioactive compounds in foods, such as polyphenols. Cocoa is a rich source of polyphenols, but its role in DNA methylation is still unknown. The objective was to assess the effect of cocoa consumption on DNA methylation and to determine whether the enzymes involved in the DNA methylation process participate in the mechanisms by which cocoa exerts these effects in humans. The global DNA methylation levels in the peripheral blood were evaluated in 214 volunteers who were pre-hypertensive, stage-1 hypertensive or hypercholesterolemic. The volunteers were divided into two groups: 110 subjects who consumed cocoa (6 g/d) for two weeks and 104 control subjects. In addition, the peripheral blood mononuclear cells (PBMCs) from six subjects were treated with a cocoa extract to analyze the mRNA levels of the DNA methyltransferases (DNMTs), methylenetetrahydrofolate reductase (MTHFR), and methionine synthase reductase (MTRR) genes. Cocoa consumption significantly reduced the DNA methylation levels (2.991±0.366 vs. 3.909±0.380, p<0.001). Additionally, we found an association between the cocoa effects on DNA methylation and three polymorphisms located in the MTHFR, MTRR, and DNMT3B genes. Furthermore, in PBMCs, the cocoa extract significantly lowered the mRNA levels of the DNMTs, MTHFR, and MTRR. Our study demonstrates for the first time that the consumption of cocoa decreases the global DNA methylation of peripheral leukocytes in humans with cardiovascular risk factors. In vitro experiments with PBMCs suggest that cocoa may exert this effect partially via the down-regulation of DNMTs, MTHFR and MTRR, which are key genes involved in this epigenetic process. Clinicaltrials.govNCT00511420 and NCT00502047.

WELDING METHOD

DOEpatents

Cornell, A.A.; Dunbar, J.V.; Ruffner, J.H.

1959-09-29

A semi-automatic method is described for the weld joining of pipes and fittings which utilizes the inert gasshielded consumable electrode electric arc welding technique, comprising laying down the root pass at a first peripheral velocity and thereafter laying down the filler passes over the root pass necessary to complete the weld by revolving the pipes and fittings at a second peripheral velocity different from the first peripheral velocity, maintaining the welding head in a fixed position as to the specific direction of revolution, while the longitudinal axis of the welding head is disposed angularly in the direction of revolution at amounts between twenty minutas and about four degrees from the first position.

Comparison of two scanning instruments to measure peripheral refraction in the human eye.

PubMed

Jaeken, Bart; Tabernero, Juan; Schaeffel, Frank; Artal, Pablo

2012-03-01

To better understand how peripheral refraction affects development of myopia in humans, specialized instruments are fundamental for precise and rapid measurements of refraction over the visual field. We compare here two prototype instruments that measure in a few seconds the peripheral refraction in the eye with high angular resolution over a range of about ±45 deg. One instrument is based on the continuous recording of Hartmann-Shack (HS) images (HS scanner) and the other is based on the photorefraction (PR) principle (PR scanner). On average, good correlations were found between the refraction results provided by the two devices, although it varied across subjects. A detailed statistical analysis of the differences between both instruments was performed based on measurements in 35 young subjects. Both instruments have advantages and disadvantages. The HS scanner also provides the high-order aberration data, while the PR scanner is more compact and has a lower cost. Both instruments are current prototypes, and further optimization is possible to make them even more suitable tools for future visual optics and myopia research and also for different ophthalmic applications.

CNS infiltration of peripheral immune cells: D-Day for neurodegenerative disease?

PubMed

Rezai-Zadeh, Kavon; Gate, David; Town, Terrence

2009-12-01

While the central nervous system (CNS) was once thought to be excluded from surveillance by immune cells, a concept known as "immune privilege," it is now clear that immune responses do occur in the CNS-giving rise to the field of neuroimmunology. These CNS immune responses can be driven by endogenous (glial) and/or exogenous (peripheral leukocyte) sources and can serve either productive or pathological roles. Recent evidence from mouse models supports the notion that infiltration of peripheral monocytes/macrophages limits progression of Alzheimer's disease pathology and militates against West Nile virus encephalitis. In addition, infiltrating T lymphocytes may help spare neuronal loss in models of amyotrophic lateral sclerosis. On the other hand, CNS leukocyte penetration drives experimental autoimmune encephalomyelitis (a mouse model for the human demyelinating disease multiple sclerosis) and may also be pathological in both Parkinson's disease and human immunodeficiency virus encephalitis. A critical understanding of the cellular and molecular mechanisms responsible for trafficking of immune cells from the periphery into the diseased CNS will be key to target these cells for therapeutic intervention in neurodegenerative diseases, thereby allowing neuroregenerative processes to ensue.

Induction of suppressor cells from peripheral blood T cells by 15-hydroperoxyeicosatetraenoic acid (15-HPETE).

PubMed

Gualde, N; Rigaud, M; Goodwin, J S

1985-11-01

15-hydroperoxyeicosetetraenoic acid (15-HPETE), a lipoxygenase metabolite of arachidonic acid, inhibited polyclonal IgG and IgM production in pokeweed mitogen (PWM)-stimulated cultures of human peripheral blood mononuclear cells, whereas 15-hydroxyeicosetetraenoic acid (15-HETE) had little effect in this system. T cells preincubated for 18 hr with 15-HPETE caused substantial inhibition of IgG and IgM production of fresh, autologous B and T cells stimulated by PWM. The suppressive effect of the 15-HPETE-treated cells was lost if the cells were irradiated before the PWM culture, but not by treatment with mitomycin C. The suppressive effect was also lost if OKT8+ T cells were removed after, but not before, preincubation of the T cells with 15-HPETE. OKT8- T cells incubated with 15-HPETE for 18 hr showed a large increase in the percentage of cells staining with directly fluoresceinated Leu-2, another marker for suppressor cells. Thus, 15-HPETE induces functional and phenotypic suppressor cells from resting human peripheral blood T cells.

Low-grade inflammation disrupts structural plasticity in the human brain.

PubMed

Szabó, C; Kelemen, O; Kéri, S

2014-09-05

Increased low-grade inflammation is thought to be associated with several neuropsychiatric disorders characterized by decreased neuronal plasticity. The purpose of the present study was to investigate the relationship between structural changes in the human brain during cognitive training and the intensity of low-grade peripheral inflammation in healthy individuals (n=56). A two-month training (30 min/day) with a platformer video game resulted in a significantly increased volume of the right hippocampal formation. The number of stressful life events experienced during the past year was associated with less pronounced enlargement of the hippocampus. However, the main predictor of hippocampal volume expansion was the relative peripheral expression of Nuclear Factor-κB (NF-κB), a transcription factor playing a central role in the effect of pro-inflammatory cytokines. Interleukin-6 (IL-6) and C-reactive protein levels were not related to hippocampal plasticity when NF-κB was taken into consideration. These results suggest that more intensive peripheral inflammation is associated with weaker neuronal plasticity during cognitive training. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

A Brain for Speech. Evolutionary Continuity in Primate and Human Auditory-Vocal Processing

PubMed Central

Aboitiz, Francisco

2018-01-01

In this review article, I propose a continuous evolution from the auditory-vocal apparatus and its mechanisms of neural control in non-human primates, to the peripheral organs and the neural control of human speech. Although there is an overall conservatism both in peripheral systems and in central neural circuits, a few changes were critical for the expansion of vocal plasticity and the elaboration of proto-speech in early humans. Two of the most relevant changes were the acquisition of direct cortical control of the vocal fold musculature and the consolidation of an auditory-vocal articulatory circuit, encompassing auditory areas in the temporoparietal junction and prefrontal and motor areas in the frontal cortex. This articulatory loop, also referred to as the phonological loop, enhanced vocal working memory capacity, enabling early humans to learn increasingly complex utterances. The auditory-vocal circuit became progressively coupled to multimodal systems conveying information about objects and events, which gradually led to the acquisition of modern speech. Gestural communication accompanies the development of vocal communication since very early in human evolution, and although both systems co-evolved tightly in the beginning, at some point speech became the main channel of communication. PMID:29636657

Decreased human immunodeficiency virus type 1 plasma viremia during antiretroviral therapy reflects downregulation of viral replication in lymphoid tissue.

PubMed Central

Cohen, O J; Pantaleo, G; Holodniy, M; Schnittman, S; Niu, M; Graziosi, C; Pavlakis, G N; Lalezari, J; Bartlett, J A; Steigbigel, R T

1995-01-01

Although several immunologic and virologic markers measured in peripheral blood are useful for predicting accelerated progression of human immunodeficiency virus (HIV) disease, their validity for evaluating the response to antiretroviral therapy and their ability to accurately reflect changes in lymphoid organs remain unclear. In the present study, changes in certain virologic markers have been analyzed in peripheral blood and lymphoid tissue during antiretroviral therapy. Sixteen HIV-infected individuals who were receiving antiretroviral therapy with zidovudine for > or = 6 months were randomly assigned either to continue on zidovudine alone or to add didanosine for 8 weeks. Lymph node biopsies were performed at baseline and after 8 weeks. Viral burden (i.e., HIV DNA copies per 10(6) mononuclear cells) and virus replication in mononuclear cells isolated from peripheral blood and lymph node and plasma viremia were determined by semiquantitative polymerase chain reaction assays. Virologic and immunologic markers remained unchanged in peripheral blood and lymph node of patients who continued on zidovudine alone. In contrast, a decrease in virus replication in lymph nodes was observed in four of six patients who added didanosine to their regimen, and this was associated with a decrease in plasma viremia. These results indicate that decreases in plasma viremia detected during antiretroviral therapy reflect downregulation of virus replication in lymphoid tissue. Images Fig. 1 Fig. 2 Fig. 3 PMID:7597072

[Combination surgery for wet age-related macular degeneration and chronic peripheral uveitis].

PubMed

Zapuskalov, I V; Krivosheina, O I; Khoroshikh, Yu I

2016-01-01

To develop a combination surgery for wet age-related macular degeneration and concurrent chronic peripheral uveitis that would include intravitreal injection of Lucentis and cryocerclage of the peripheral retina. A total of 75 patients were examined and divided into 2 groups: the main group (37 patients) and the controls (38 patients). Patients from the main group underwent the new combination surgery, while the controls received intravitreal Lucentis alone (peripheral uveitis was managed therapeutically). It has been found that the new combination method provides a significant and stable improvement in visual acuity (by a factor of 10) and a decrease in the area of central scotoma (by a factor of 2.95) in the postoperative period. The period needed for recovery in the central retinal thickness is also 1.6 times shorter. The new combination surgery for wet age-related macular degeneration and concurrent chronic peripheral uveitis provides rapid reduction of inflammation in the extreme periphery of the fundus and a 1.5 times faster (as compared to traditional methods) primary restoration of topographic anatomy of the retina in the macular region.

Influence of Rotator Cuff Tear Size and Repair Technique on the Creation and Management of Dog Ear Deformities in a Transosseous-Equivalent Rotator Cuff Repair Model

PubMed Central

Redler, Lauren H.; Byram, Ian R.; Luchetti, Timothy J.; Tsui, Ying Lai; Moen, Todd C.; Gardner, Thomas R.; Ahmad, Christopher S.

2014-01-01

Background: Redundancies in the rotator cuff tissue, commonly referred to as “dog ear” deformities, are frequently encountered during rotator cuff repair. Knowledge of how these deformities are created and their impact on rotator cuff footprint restoration is limited. Purpose: The goals of this study were to assess the impact of tear size and repair method on the creation and management of dog ear deformities in a human cadaveric model. Study Design: Controlled laboratory study. Methods: Crescent-shaped tears were systematically created in the supraspinatus tendon of 7 cadaveric shoulders with increasing medial to lateral widths (0.5, 1.0, and 1.5 cm). Repair of the 1.5-cm tear was performed on each shoulder with 3 methods in a randomized order: suture bridge, double-row repair with 2-mm fiber tape, and fiber tape with peripheral No. 2 nonabsorbable looped sutures. Resulting dog ear deformities were injected with an acrylic resin mixture, digitized 3-dimensionally (3D), and photographed perpendicular to the footprint with calibration. The volume, height, and width of the rotator cuff tissue not in contact with the greater tuberosity footprint were calculated using the volume injected, 3D reconstructions, and calibrated photographs. Comparisons were made between tear size, dog ear measurement technique, and repair method utilizing 2-way analysis of variance and Student-Newman-Keuls multiple-comparison tests. Results: Utilizing 3D digitized and injection-derived volumes and dimensions, anterior dog ear volume, height, and width were significantly smaller for rotator cuff repair with peripheral looped sutures compared with a suture bridge (P < .05) or double-row repair with 2-mm fiber tape alone (P < .05). Similarly, posterior height and width were significantly smaller for repair with looped peripheral sutures compared with a suture bridge (P < .05). Dog ear volumes and heights trended larger for the 1.5-cm tear, but this was not statistically significant. Conclusion: When combined with a standard transosseous-equivalent repair technique, peripheral No. 2 nonabsorbable looped sutures significantly decreased the volume, height, and width of dog ear deformities, better restoring the anatomic footprint of the rotator cuff. Clinical Relevance: Dog ear deformities are commonly encountered during rotator cuff repair. Knowledge of a repair technique that reliably decreases their size, and thus increases contact at the anatomic footprint of the rotator cuff, will aid sports medicine surgeons in the management of these deformities. PMID:26535317

A voltage-controlled capacitive discharge method for electrical activation of peripheral nerves.

PubMed

Rosellini, Will M; Yoo, Paul B; Engineer, Navzer; Armstrong, Scott; Weiner, Richard L; Burress, Chester; Cauller, Larry

2011-01-01

A voltage-controlled capacitive discharge (VCCD) method was investigated as an alternative to rectangular stimulus pulses currently used in peripheral nerve stimulation therapies.  In two anesthetized Gottingen mini pigs, the threshold (total charge per phase) for evoking a compound nerve action potential (CNAP) was compared between constant current (CC) and VCCD methods. Electrical pulses were applied to the tibial and posterior cutaneous femoralis nerves using standard and modified versions of the Medtronic 3778 Octad.  In contrast to CC stimulation, the combined application of VCCD pulses with a modified Octad resulted in a marked decrease (-73 ± 7.4%) in the stimulation threshold for evoking a CNAP. This was consistent for different myelinated fiber types and locations of stimulation.  The VCCD method provides a highly charge-efficient means of activating myelinated fibers that could potentially be used within a wireless peripheral nerve stimulator system. © 2011 International Neuromodulation Society.

Impaired human responses to tetanus toxoid in vitamin A-deficient SCID mice reconstituted with human peripheral blood lymphocytes.

PubMed Central

Molrine, D C; Polk, D B; Ciamarra, A; Phillips, N; Ambrosino, D M

1995-01-01

Vitamin A deficiency is associated with increased childhood morbidity and mortality from respiratory and diarrheal diseases. In order to evaluate the effect of vitamin A on human antibody responses, we developed a vitamin A-deficient severe combined immunodeficient (SCID) mouse model. Vitamin A-deficient mice were produced by depriving them of vitamin A at day 7 of gestation. Mice were reconstituted with human peripheral blood lymphocytes (huPBL) from tetanus toxoid immune donors at 6 weeks of age and immunized with tetanus toxoid at 6 and 8 weeks of age. Secondary human antibody responses were determined 10 days later. The geometric mean human anti-tetanus toxoid immunoglobulin G concentrations were 3.75 micrograms/ml for the deficient mice and 148 micrograms/ml for controls (P = 0.0005). Vitamin A-deficient mice had only a 2.9-fold increase in human anti-tetanus toxoid antibody compared with a 74-fold increase in controls (P < 0.01). Supplementation with vitamin A prior to reconstitution restored human antibody responses to normal. These data suggest that vitamin A deficiency impairs human antibody responses. We speculate that impaired responses could increase susceptibility to certain infections. Furthermore, we propose that effects of other nutritional deficiencies on the human immune system could be evaluated in the SCID-huPBL model. PMID:7622207

Electrophysiological measurement of human auditory function

NASA Technical Reports Server (NTRS)

Galambos, R.

1975-01-01

Knowledge of the human auditory evoked response is reviewed, including methods of determining this response, the way particular changes in the stimulus are coupled to specific changes in the response, and how the state of mind of the listener will influence the response. Important practical applications of this basic knowledge are discussed. Measurement of the brainstem evoked response, for instance, can state unequivocally how well the peripheral auditory apparatus functions. It might then be developed into a useful hearing test, especially for infants and preverbal or nonverbal children. Clinical applications of measuring the brain waves evoked 100 msec and later after the auditory stimulus are undetermined. These waves are clearly related to brain events associated with cognitive processing of acoustic signals, since their properties depend upon where the listener directs his attention and whether how long he expects the signal.

The expression and significance of T helper cell subsets and regulatory T cells CD₄⁺ CD₂₅⁺ in peripheral blood of patients with human leukocyte antigen B27-positive acute anterior uveitis.

PubMed

Zou, Wenjun; Wu, Zhifeng; Xiang, Xiaoli; Sun, Song; Zhang, Jie

2014-04-01

Human leukocyte antigen B27 (HLA-B27)-associated uveitis is the most common reason for non-infectious uveitis. This purpose of the research was to study the expression and significance of T lymphocyte subsets and CD₄⁺ CD₂₅⁺ T regulatory (Treg) cells in peripheral blood of patients with Human leukocyte antigen B27-positive acute anterior uveitis (HLA-B27-positive AAU). The concentrations of Th1, Th2, Th17, CD₄⁺ CD₂₅⁺and CD₄⁺ CD₂₅⁺FOXP3⁺ Treg cells in peripheral blood were tested by flow cytometry. C-reactive protein (CRP) in peripheral blood was detected by immunoturbidimetry (ITM). Spearman's rank correlation was used to analyze the relationships between the concentration of Th1, Th2, Th17, CD₄⁺ CD₂₅⁺, and CD₄⁺ CD₂₅⁺ FOXP3(+) Treg cells in peripheral blood and disease activity score and CRP content. The ratio of both γ [interferon (IFN)-γ] (+)CD4⁺Th1 cells and CD4⁺IL-17⁺Th17 cells in peripheral blood of patients with HLA-B27-positive AAU (P = 0.041) was higher than that of the control group (P = 0.002). The concentration of CD₄⁺ CD₂₅⁺ FOXP3(+) T cells in peripheral blood of patients with AAU was lower than that of the control group (P = 0.026). The concentration of Th1 cells in peripheral blood of the patients had no correlation with disease activity score (P = 0.50) or CRP content (P = 0.383). This was also true of the concentration of Th2 cells (Disease activity score: R = 0.068, P = 0.817; CRP content: R = 0.439, P = 0.116). Th17 cell concentration positively correlated with disease activity score (R = 0.805, P = 0.001). The concentration of CD₄⁺ CD₂₅⁺ T cells showed no correlation with disease activity score (R =-0.209, P = 0.472) or CRP content (R =-0.169, P = 0.563), whereas the concentration of CD4⁺ CD25⁺ FOXP3⁺ T cells negatively correlated with disease activity score but did not correlate with CRP (R =-0.248, P = 0.392). The peripheral blood of patients with HLA-B27-positive AAU showed a higher expression of interferon-γ and interleukin-17 cells in CD4⁺T cells, whereas CD4⁺CD25⁺FOXP3⁺ T cells displayed a lower expression of the cytokines. The balance between Th17 cells and CD4⁺  CD25⁺  FOXP3⁺ T cells may contribute to the activity of HLA-B27-positive AAU.

Change in peripheral refraction and curvature of field of the human eye with accommodation

NASA Astrophysics Data System (ADS)

Ho, Arthur; Zimmermann, Frederik; Whatham, Andrew; Martinez, Aldo; Delgado, Stephanie; Lazon de la Jara, Percy; Sankaridurg, Padmaja

2009-02-01

Recent research showed that the peripheral refractive state is a sufficient stimulus for myopia progression. This finding led to the suggestion that devices that control peripheral refraction may be efficacious in controlling myopia progression. This study aims to understand whether the optical effect of such devices may be affected by near focus. In particular, we seek to understand the influence of accommodation on peripheral refraction and curvature of field of the eye. Refraction was measured in twenty young subjects using an autorefractor at 0° (i.e. along visual axis), and 20°, 30° and 40° field angles both nasal and temporal to the visual axis. All measurements were conducted at 2.5 m, 40 cm and 30 cm viewing distances. Refractive errors were corrected using a soft contact lens during all measurements. As field angle increased, refraction became less hyperopic. Peripheral refraction also became less hyperopic at nearer viewing distances (i.e. with increasing accommodation). Astigmatism (J180) increased with field angle as well as with accommodation. Adopting a third-order aberration theory approach, the position of the Petzval surface relative to the retinal surface was estimated by considering the relative peripheral refractive error (RPRE) and J180 terms of peripheral refraction. Results for the estimated dioptric position of the Petzval surface relative to the retina showed substantial asymmetry. While temporal field tended to agree with theoretical predictions, nasal response departed dramatically from the model eye predictions. With increasing accommodation, peripheral refraction becomes less hyperopic while the Petzval surface showed asymmetry in its change in position. The change in the optical components (i.e. cornea and/or lens as opposed to retinal shape or position) is implicated as at least one of the contributors of this shift in peripheral refraction during accommodation.

Association of diabetic peripheral arterial disease and objectively-measured physical activity: NHANES 2003-2004

PubMed Central

2014-01-01

Background Although much is known about the management of peripheral arterial disease among adults in the general population, the management of this disease among those with diabetes, and the effects of diabetic-induced peripheral arterial disease on objectively-measured physical activity, is unclear. Here, we examined the association between accelerometer-assessed physical activity and peripheral arterial disease among a national sample of U.S. adults with diabetes. Methods Data from the 2003–2004 National Health and Nutrition Examination Survey were used. Physical activity was measured using an accelerometer in 254 adults with diabetes. Peripheral arterial disease was assessed via ankle brachial index. Negative binomial regression analysis was used to examine the association between physical activity and peripheral arterial disease. Results Results were adjusted for age, gender, race-ethnicity, comorbidity index, smoking, HgbA1C, C-reactive protein, homocysteine, glomerular filtration rate, microalbuminuria, peripheral neuropathy, physical functioning, and medication use. After adjustments, participants with peripheral arterial disease engaged in 23% less physical activity (RR = 0.77, 95% CI: 0.62-0.96) than those without peripheral arterial disease. Conclusions These findings demonstrate an inverse association between accelerometer-assessed physical activity and peripheral arterial disease in a national sample of U.S adults with diabetes. PMID:24967220

A simplified sheathless cell separation approach using combined gravitational-sedimentation-based prefocusing and dielectrophoretic separation.

PubMed

Luo, Tao; Fan, Lei; Zeng, Yixiao; Liu, Ya; Chen, Shuxun; Tan, Qiulin; Lam, Raymond H W; Sun, Dong

2018-05-04

Prefocusing of the cell mixture is necessary for achieving a high-efficiency and continuous dielectrophoretic (DEP) cell separation. However, prefocusing through sheath flow requires a complex and tedious peripheral system for multi-channel fluid control, hindering the integration of DEP separation systems with other microfluidic functionalities for comprehensive clinical and biological tasks. This paper presented a simplified sheathless cell separation approach that combines gravitational-sedimentation-based sheathless prefocusing and DEP separation methods. Through gravitational sedimentation in a tubing, which was inserted into the inlet of a microfluidic chip with an adjustable steering angle, the cells were focused into a stream at the upstream region of a microchannel prior to separation. Then, a DEP force was applied at the downstream region of the microchannel for the active separation of the cells. Through this combined strategy, the peripheral system for the sheath flow was no longer required, and thus the integration of cell separation system with additional microfluidic functionalities was facilitated. The proposed sheathless scheme focused the mixture of cells with different sizes and dielectric properties into a stream in a wide range of flow rates without changing the design of the microfluidic chip. The DEP method is a label-free approach that can continuously separate cells on the basis of the sizes or dielectric properties of the cells and thus capable of greatly flexible cell separation. The efficiency of the proposed approach was experimentally assessed according to its performance in the separation of human acute monocytic leukemia THP-1 cells from yeast cells with respect to different sizes and THP-1 cells from human acute myelomonocytic leukemia OCI-AML3 cells with respect to different dielectric properties. The experimental results revealed that the separation efficiency of the method can surpass 90% and thus effective in separating cells on the basis of either size or dielectric property.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tamburello, David A.; McWilliams, Anthony J.; Hardy, Bruce J.

Vessel assemblies, heat transfer units for prefabricated vessels, and methods for heat transfer prefabricated vessel are provided. A heat transfer unit includes a central rod, and a plurality of peripheral rods surrounding the central rod and connected to the central rod. The plurality of peripheral rods are movable between a first collapsed position and a second bowed position, wherein in the second bowed position a midpoint of each of the plurality of peripheral rods is spaced from the central rod relative to in the first position. The heat transfer unit further includes a heat transfer element connected to one ofmore » the plurality of peripheral rods.« less

Impact of Morphometry, Myelinization and Synaptic Current Strength on Spike Conduction in Human and Cat Spiral Ganglion Neurons

PubMed Central

Rattay, Frank; Potrusil, Thomas; Wenger, Cornelia; Wise, Andrew K.; Glueckert, Rudolf; Schrott-Fischer, Anneliese

2013-01-01

Background Our knowledge about the neural code in the auditory nerve is based to a large extent on experiments on cats. Several anatomical differences between auditory neurons in human and cat are expected to lead to functional differences in speed and safety of spike conduction. Methodology/Principal Findings Confocal microscopy was used to systematically evaluate peripheral and central process diameters, commonness of myelination and morphology of spiral ganglion neurons (SGNs) along the cochlea of three human and three cats. Based on these morphometric data, model analysis reveales that spike conduction in SGNs is characterized by four phases: a postsynaptic delay, constant velocity in the peripheral process, a presomatic delay and constant velocity in the central process. The majority of SGNs are type I, connecting the inner hair cells with the brainstem. In contrast to those of humans, type I neurons of the cat are entirely myelinated. Biophysical model evaluation showed delayed and weak spikes in the human soma region as a consequence of a lack of myelin. The simulated spike conduction times are in accordance with normal interwave latencies from auditory brainstem response recordings from man and cat. Simulated 400 pA postsynaptic currents from inner hair cell ribbon synapses were 15 times above threshold. They enforced quick and synchronous spiking. Both of these properties were not present in type II cells as they receive fewer and much weaker (∼26 pA) synaptic stimuli. Conclusions/Significance Wasting synaptic energy boosts spike initiation, which guarantees the rapid transmission of temporal fine structure of auditory signals. However, a lack of myelin in the soma regions of human type I neurons causes a large delay in spike conduction in comparison with cat neurons. The absent myelin, in combination with a longer peripheral process, causes quantitative differences of temporal parameters in the electrically stimulated human cochlea compared to the cat cochlea. PMID:24260179

Numerosity estimation benefits from transsaccadic information integration

PubMed Central

Hübner, Carolin; Schütz, Alexander C.

2017-01-01

Humans achieve a stable and homogeneous representation of their visual environment, although visual processing varies across the visual field. Here we investigated the circumstances under which peripheral and foveal information is integrated for numerosity estimation across saccades. We asked our participants to judge the number of black and white dots on a screen. Information was presented either in the periphery before a saccade, in the fovea after a saccade, or in both areas consecutively to measure transsaccadic integration. In contrast to previous findings, we found an underestimation of numerosity for foveal presentation and an overestimation for peripheral presentation. We used a maximum-likelihood model to predict accuracy and reliability in the transsaccadic condition based on peripheral and foveal values. We found near-optimal integration of peripheral and foveal information, consistently with previous findings about orientation integration. In three consecutive experiments, we disrupted object continuity between the peripheral and foveal presentations to probe the limits of transsaccadic integration. Even for global changes on our numerosity stimuli, no influence of object discontinuity was observed. Overall, our results suggest that transsaccadic integration is a robust mechanism that also works for complex visual features such as numerosity and is operative despite internal or external mismatches between foveal and peripheral information. Transsaccadic integration facilitates an accurate and reliable perception of our environment. PMID:29149766

Clock-Talk: Interactions between Central and Peripheral Circadian Oscillators in Mammals.

PubMed

Schibler, Ueli; Gotic, Ivana; Saini, Camille; Gos, Pascal; Curie, Thomas; Emmenegger, Yann; Sinturel, Flore; Gosselin, Pauline; Gerber, Alan; Fleury-Olela, Fabienne; Rando, Gianpaolo; Demarque, Maud; Franken, Paul

2015-01-01

In mammals, including humans, nearly all physiological processes are subject to daily oscillations that are governed by a circadian timing system with a complex hierarchical structure. The central pacemaker, residing in the suprachiasmatic nucleus (SCN) of the ventral hypothalamus, is synchronized daily by photic cues transmitted from the retina to SCN neurons via the retinohypothalamic tract. In turn, the SCN must establish phase coherence between self-sustained and cell-autonomous oscillators present in most peripheral cell types. The synchronization signals (Zeitgebers) can be controlled more or less directly by the SCN. In mice and rats, feeding-fasting rhythms, which are driven by the SCN through rest-activity cycles, are the most potent Zeitgebers for the circadian oscillators of peripheral organs. Signaling through the glucocorticoid receptor and the serum response factor also participate in the phase entrainment of peripheral clocks, and these two pathways are controlled by the SCN independently of feeding-fasting rhythms. Body temperature rhythms, governed by the SCN directly and indirectly through rest-activity cycles, are perhaps the most surprising cues for peripheral oscillators. Although the molecular makeup of circadian oscillators is nearly identical in all cells, these oscillators are used for different purposes in the SCN and in peripheral organs. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

Electromagnetic Navigation Diagnostic Bronchoscopy

PubMed Central

Gildea, Thomas R.; Mazzone, Peter J.; Karnak, Demet; Meziane, Moulay; Mehta, Atul C.

2006-01-01

Rationale: Electromagnetic navigation bronchoscopy using superDimension/Bronchus System is a novel method to increase diagnostic yield of peripheral and mediastinal lung lesions. Objectives: A prospective, open label, single-center, pilot study was conducted to determine the ability of electromagnetic navigation bronchoscopy to sample peripheral lung lesions and mediastinal lymph nodes with standard bronchoscopic instruments and demonstrate safety. Methods: Electromagnetic navigation bronchoscopy was performed using the superDimension/Bronchus system consisting of electromagnetic board, position sensor encapsulated in the tip of a steerable probe, extended working channel, and real-time reconstruction of previously acquired multiplanar computed tomography images. The final distance of the steerable probe to lesion, expected error based on the actual and virtual markers, and procedure yield was gathered. Measurements: 60 subjects were enrolled between December 2004 and September 2005. Mean navigation times were 7 ± 6 min and 2 ± 2 min for peripheral lesions and lymph nodes, respectively. The steerable probe tip was navigated to the target lung area in all cases. The mean peripheral lesions and lymph nodes size was 22.8 ± 12.6 mm and 28.1 ± 12.8 mm. Yield was determined by results obtained during the bronchoscopy per patient. Results: The yield/procedure was 74% and 100% for peripheral lesions and lymph nodes, respectively. A diagnosis was obtained in 80.3% of bronchoscopic procedures. A definitive diagnosis of lung malignancy was made in 74.4% of subjects. Pneumothorax occurred in two subjects. Conclusion: Electromagnetic navigation bronchoscopy is a safe method for sampling peripheral and mediastinal lesions with high diagnostic yield independent of lesion size and location. PMID:16873767

Bio-inspired approach for intelligent unattended ground sensors

NASA Astrophysics Data System (ADS)

Hueber, Nicolas; Raymond, Pierre; Hennequin, Christophe; Pichler, Alexander; Perrot, Maxime; Voisin, Philippe; Moeglin, Jean-Pierre

2015-05-01

Improving the surveillance capacity over wide zones requires a set of smart battery-powered Unattended Ground Sensors capable of issuing an alarm to a decision-making center. Only high-level information has to be sent when a relevant suspicious situation occurs. In this paper we propose an innovative bio-inspired approach that mimics the human bi-modal vision mechanism and the parallel processing ability of the human brain. The designed prototype exploits two levels of analysis: a low-level panoramic motion analysis, the peripheral vision, and a high-level event-focused analysis, the foveal vision. By tracking moving objects and fusing multiple criteria (size, speed, trajectory, etc.), the peripheral vision module acts as a fast relevant event detector. The foveal vision module focuses on the detected events to extract more detailed features (texture, color, shape, etc.) in order to improve the recognition efficiency. The implemented recognition core is able to acquire human knowledge and to classify in real-time a huge amount of heterogeneous data thanks to its natively parallel hardware structure. This UGS prototype validates our system approach under laboratory tests. The peripheral analysis module demonstrates a low false alarm rate whereas the foveal vision correctly focuses on the detected events. A parallel FPGA implementation of the recognition core succeeds in fulfilling the embedded application requirements. These results are paving the way of future reconfigurable virtual field agents. By locally processing the data and sending only high-level information, their energy requirements and electromagnetic signature are optimized. Moreover, the embedded Artificial Intelligence core enables these bio-inspired systems to recognize and learn new significant events. By duplicating human expertise in potentially hazardous places, our miniature visual event detector will allow early warning and contribute to better human decision making.

Chemical nature and immunotoxicological properties of arachidonic acid degradation products formed by exposure to ozone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Madden, M.C.; Friedman, M.; Hanley, N.

1993-06-01

Ozone (O3) exposure in vivo has been reported to degrade arachidonic acid (AA) in the lungs of rodents. The O3-degraded AA products may play a role in the responses to this toxicant. To study the chemical nature and biological activity of O3-exposed AA, we exposed AA in a cell-free, aqueous environment to air, 0.1 ppm O3, or 1.0 ppm O3 for 30-120 min. AA exposed to air was not degraded. All O3 exposures degraded > 98% of the AA to more polar products, which were predominantly aldehydic substances (as determined by reactivity with 2,4-dinitrophenylhydrazine and subsequent separation by HPLC) andmore » hydrogen peroxide. The type and amount of aldehydic substances formed depended on the O3 concentration and exposure duration. A human bronchial epithelial cell line (BEAS-2B, S6 subclone) exposed in vitro to either 0.1 ppm or 1.0 ppm O3 for 1 hr produced AA-derived aldehydic substances, some of which eluted with similar retention times as the aldehydic substances derived from O3 degradation of AA in the cell-free system. In vitro, O3-degraded AA induced an increase in human peripheral blood polymorphonuclear leukocyte (PMN) polarization, decreased human peripheral blood T-lymphocyte proliferation in response to mitogens, and decreased human peripheral blood natural killer cell lysis of K562 target cells. The aldehydic substances, but not hydrogen peroxide, appeared to be the principal active agents responsible for the observed effects. O3-degraded AA may play a role in the PMN influx into lungs and in decreased T-lymphocyte mitogenesis and natural killer cell activity observed in humans and rodents exposed to O3.« less

Ultrastructural study on the retinal pigment epithelium of human embryos, with special reference to quantitative study on the development of melanin granules.

PubMed

Oguni, M; Tanaka, O; Shinohara, H; Yoshioka, T; Setogawa, T

1991-01-01

The development of the retinal pigment epithelium (RPE) was studied ultrastructurally, using 13 externally normal human embryos, Carnegie stages ranging from 13 to 23 (4-8 week of gestation). Melanosomes in the peripheral and posterior RPE were classified according to Fitzpatrick et al. The melanosome of phase I is formed from the Golgi complex and parcelled off into small vesicles. The vesicle enlarges and elongates to form an oval organelle with membranous structures in it (phase II melanosome). Subsequently, melanin deposits on the membranous structures of the melanosomes (phase III melanosomes), and the completion of this process produces a uniformly electrondense granule without discernible internal structures (phase IV melanosome). Melanosomes of phases III and IV appeared in the RPE at stage 15. As the embryonic stage advanced, the ratio of phase II melanosomes decreased and that of phase IV melanosomes increased. The number of phase III melanosomes reached a peak in the peripheral and posterior RPE at stages 15 and 18, respectively. After stage 17, the increase in melanosomes and intracellular organelles was more prominent in the posterior than in the peripheral RPE. During stages 13 and 15, gap junctions were present not only in the apical but also basal plasma membranes of the RPE. At stage 20, gap junctions in the basal plasma membrane disappeared except for the transitional areas from the RPE to the neural retina (NR). In addition, gap junctions were observed between NR and RPE only in the peripheral region at stage 20. The morphological and quantitative differences in the peripheral and posterior RPE in the embryonic period are discussed.

Regenerative effects of human embryonic stem cell-derived neural crest cells for treatment of peripheral nerve injury.

PubMed

Jones, Iwan; Novikova, Liudmila N; Novikov, Lev N; Renardy, Monika; Ullrich, Andreas; Wiberg, Mikael; Carlsson, Leif; Kingham, Paul J

2018-04-01

Surgical intervention is the current gold standard treatment following peripheral nerve injury. However, this approach has limitations, and full recovery of both motor and sensory modalities often remains incomplete. The development of artificial nerve grafts that either complement or replace current surgical procedures is therefore of paramount importance. An essential component of artificial grafts is biodegradable conduits and transplanted cells that provide trophic support during the regenerative process. Neural crest cells are promising support cell candidates because they are the parent population to many peripheral nervous system lineages. In this study, neural crest cells were differentiated from human embryonic stem cells. The differentiated cells exhibited typical stellate morphology and protein expression signatures that were comparable with native neural crest. Conditioned media harvested from the differentiated cells contained a range of biologically active trophic factors and was able to stimulate in vitro neurite outgrowth. Differentiated neural crest cells were seeded into a biodegradable nerve conduit, and their regeneration potential was assessed in a rat sciatic nerve injury model. A robust regeneration front was observed across the entire width of the conduit seeded with the differentiated neural crest cells. Moreover, the up-regulation of several regeneration-related genes was observed within the dorsal root ganglion and spinal cord segments harvested from transplanted animals. Our results demonstrate that the differentiated neural crest cells are biologically active and provide trophic support to stimulate peripheral nerve regeneration. Differentiated neural crest cells are therefore promising supporting cell candidates to aid in peripheral nerve repair. © 2018 The Authors. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons, Ltd.

Wide-field retinal optical coherence tomography with wavefront sensorless adaptive optics for enhanced imaging of targeted regions.

PubMed

Polans, James; Keller, Brenton; Carrasco-Zevallos, Oscar M; LaRocca, Francesco; Cole, Elijah; Whitson, Heather E; Lad, Eleonora M; Farsiu, Sina; Izatt, Joseph A

2017-01-01

The peripheral retina of the human eye offers a unique opportunity for assessment and monitoring of ocular diseases. We have developed a novel wide-field (>70°) optical coherence tomography system (WF-OCT) equipped with wavefront sensorless adaptive optics (WSAO) for enhancing the visualization of smaller (<25°) targeted regions in the peripheral retina. We iterated the WSAO algorithm at the speed of individual OCT B-scans (~20 ms) by using raw spectral interferograms to calculate the optimization metric. Our WSAO approach with a 3 mm beam diameter permitted primarily low- but also high- order peripheral wavefront correction in less than 10 seconds. In preliminary imaging studies in five normal human subjects, we quantified statistically significant changes with WSAO correction, corresponding to a 10.4% improvement in average pixel brightness (signal) and 7.0% improvement in high frequency content (resolution) when visualizing 1 mm (~3.5°) B-scans of the peripheral (>23°) retina. We demonstrated the ability of our WF-OCT system to acquire non wavefront-corrected wide-field images rapidly, which could then be used to locate regions of interest, zoom into targeted features, and visualize the same region at different time points. A pilot clinical study was conducted on seven healthy volunteers and two subjects with prodromal Alzheimer's disease which illustrated the capability to image Drusen-like pathologies as far as 32.5° from the fovea in un-averaged volume scans. This work suggests that the proposed combination of WF-OCT and WSAO may find applications in the diagnosis and treatment of ocular, and potentially neurodegenerative, diseases of the peripheral retina, including diabetes and Alzheimer's disease.

Wide-field retinal optical coherence tomography with wavefront sensorless adaptive optics for enhanced imaging of targeted regions

PubMed Central

Polans, James; Keller, Brenton; Carrasco-Zevallos, Oscar M.; LaRocca, Francesco; Cole, Elijah; Whitson, Heather E.; Lad, Eleonora M.; Farsiu, Sina; Izatt, Joseph A.

2016-01-01

The peripheral retina of the human eye offers a unique opportunity for assessment and monitoring of ocular diseases. We have developed a novel wide-field (>70°) optical coherence tomography system (WF-OCT) equipped with wavefront sensorless adaptive optics (WSAO) for enhancing the visualization of smaller (<25°) targeted regions in the peripheral retina. We iterated the WSAO algorithm at the speed of individual OCT B-scans (~20 ms) by using raw spectral interferograms to calculate the optimization metric. Our WSAO approach with a 3 mm beam diameter permitted primarily low- but also high- order peripheral wavefront correction in less than 10 seconds. In preliminary imaging studies in five normal human subjects, we quantified statistically significant changes with WSAO correction, corresponding to a 10.4% improvement in average pixel brightness (signal) and 7.0% improvement in high frequency content (resolution) when visualizing 1 mm (~3.5°) B-scans of the peripheral (>23°) retina. We demonstrated the ability of our WF-OCT system to acquire non wavefront-corrected wide-field images rapidly, which could then be used to locate regions of interest, zoom into targeted features, and visualize the same region at different time points. A pilot clinical study was conducted on seven healthy volunteers and two subjects with prodromal Alzheimer’s disease which illustrated the capability to image Drusen-like pathologies as far as 32.5° from the fovea in un-averaged volume scans. This work suggests that the proposed combination of WF-OCT and WSAO may find applications in the diagnosis and treatment of ocular, and potentially neurodegenerative, diseases of the peripheral retina, including diabetes and Alzheimer’s disease. PMID:28101398

Threshold dose for peripheral neuropathy following intraoperative radiotherapy (IORT) in a large animal model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kinsella, T.J.; DeLuca, A.M.; Barnes, M.

1991-04-01

Radiation injury to peripheral nerve is a dose-limiting toxicity in the clinical application of intraoperative radiotherapy, particularly for pelvic and retroperitoneal tumors. Intraoperative radiotherapy-related peripheral neuropathy in humans receiving doses of 20-25 Gy is manifested as a mixed motor-sensory deficit beginning 6-9 months following treatment. In a previous experimental study of intraoperative radiotherapy-related neuropathy of the lumbro-sacral plexus, an approximate inverse linear relationship was reported between the intraoperative dose (20-75 Gy range) and the time to onset of hind limb paresis (1-12 mos following intraoperative radiotherapy). The principal histological lesion in irradiated nerve was loss of large nerve fibers andmore » perineural fibrosis without significant vascular injury. Similar histological changes in irradiated nerves were found in humans. To assess peripheral nerve injury to lower doses of intraoperative radiotherapy in this same large animal model, groups of four adult American Foxhounds received doses of 10, 15, or 20 Gy to the right lumbro-sacral plexus and sciatic nerve using 9 MeV electrons. The left lumbro-sacral plexus and sciatic nerve were excluded from the intraoperative field to allow each animal to serve as its own control. Following treatment, a complete neurological exam, electromyogram, and nerve conduction studies were performed monthly for 1 year. Monthly neurological exams were performed in years 2 and 3 whereas electromyogram and nerve conduction studies were performed every 3 months during this follow-up period. With follow-up of greater than or equal to 42 months, no dog receiving 10 or 15 Gy IORT shows any clinical or laboratory evidence of peripheral nerve injury. However, all four dogs receiving 20 Gy developed right hind limb paresis at 8, 9, 9, and 12 mos following intraoperative radiotherapy.« less

An in vitro model of Mycobacterium leprae induced granuloma formation

PubMed Central

2013-01-01

Background Leprosy is a contagious and chronic systemic granulomatous disease caused by Mycobacterium leprae. In the pathogenesis of leprosy, granulomas play a key role, however, the mechanisms of the formation and maintenance of M. leprae granulomas are still not clearly understood. Methods To better understand the molecular physiology of M. leprae granulomas and the interaction between the bacilli and human host cells, we developed an in vitro model of human granulomas, which mimicked the in vivo granulomas of leprosy. Macrophages were differentiated from human monocytes, and infected with M. leprae, and then cultured with autologous human peripheral blood mononuclear cells (PBMCs). Results Robust granuloma-like aggregates were obtained only when the M. leprae infected macrophages were co-cultured with PBMCs. Histological examination showed M. leprae within the cytoplasmic center of the multinucleated giant cells, and these bacilli were metabolically active. Macrophages of both M1 and M2 types co-existed in the granuloma like aggregates. There was a strong relationship between the formation of granulomas and changes in the expression levels of cell surface antigens on macrophages, cytokine production and the macrophage polarization. The viability of M. leprae isolated from granulomas indicated that the formation of host cell aggregates benefited the host, but the bacilli also remained metabolically active. Conclusions A simple in vitro model of human M. leprae granulomas was established using human monocyte-derived macrophages and PBMCs. This system may be useful to unravel the mechanisms of disease progression, and subsequently develop methods to control leprosy. PMID:23782413

Syndromic Algorithms for Detection of Gambiense Human African Trypanosomiasis in South Sudan

PubMed Central

Palmer, Jennifer J.; Surur, Elizeous I.; Goch, Garang W.; Mayen, Mangar A.; Lindner, Andreas K.; Pittet, Anne; Kasparian, Serena; Checchi, Francesco; Whitty, Christopher J. M.

2013-01-01

Background Active screening by mobile teams is considered the best method for detecting human African trypanosomiasis (HAT) caused by Trypanosoma brucei gambiense but the current funding context in many post-conflict countries limits this approach. As an alternative, non-specialist health care workers (HCWs) in peripheral health facilities could be trained to identify potential cases who need testing based on their symptoms. We explored the predictive value of syndromic referral algorithms to identify symptomatic cases of HAT among a treatment-seeking population in Nimule, South Sudan. Methodology/Principal Findings Symptom data from 462 patients (27 cases) presenting for a HAT test via passive screening over a 7 month period were collected to construct and evaluate over 14,000 four item syndromic algorithms considered simple enough to be used by peripheral HCWs. For comparison, algorithms developed in other settings were also tested on our data, and a panel of expert HAT clinicians were asked to make referral decisions based on the symptom dataset. The best performing algorithms consisted of three core symptoms (sleep problems, neurological problems and weight loss), with or without a history of oedema, cervical adenopathy or proximity to livestock. They had a sensitivity of 88.9–92.6%, a negative predictive value of up to 98.8% and a positive predictive value in this context of 8.4–8.7%. In terms of sensitivity, these out-performed more complex algorithms identified in other studies, as well as the expert panel. The best-performing algorithm is predicted to identify about 9/10 treatment-seeking HAT cases, though only 1/10 patients referred would test positive. Conclusions/Significance In the absence of regular active screening, improving referrals of HAT patients through other means is essential. Systematic use of syndromic algorithms by peripheral HCWs has the potential to increase case detection and would increase their participation in HAT programmes. The algorithms proposed here, though promising, should be validated elsewhere. PMID:23350005

Multiplexed mass cytometry profiling of cellular states perturbed by small-molecule regulators

PubMed Central

Bodenmiller, Bernd; Zunder, Eli R.; Finck, Rachel; Chen, Tiffany J.; Savig, Erica S.; Bruggner, Robert V.; Simonds, Erin F.; Bendall, Sean C.; Sachs, Karen; Krutzik, Peter O.; Nolan, Garry P.

2013-01-01

The ability to comprehensively explore the impact of bio-active molecules on human samples at the single-cell level can provide great insight for biomedical research. Mass cytometry enables quantitative single-cell analysis with deep dimensionality, but currently lacks high-throughput capability. Here we report a method termed mass-tag cellular barcoding (MCB) that increases mass cytometry throughput by sample multiplexing. 96-well format MCB was used to characterize human peripheral blood mononuclear cell (PBMC) signaling dynamics, cell-to-cell communication, the signaling variability between 8 donors, and to define the impact of 27 inhibitors on this system. For each compound, 14 phosphorylation sites were measured in 14 PBMC types, resulting in 18,816 quantified phosphorylation levels from each multiplexed sample. This high-dimensional systems-level inquiry allowed analysis across cell-type and signaling space, reclassified inhibitors, and revealed off-target effects. MCB enables high-content, high-throughput screening, with potential applications for drug discovery, pre-clinical testing, and mechanistic investigation of human disease. PMID:22902532

Ultrasound-guided percutaneous injection of methylene blue to identify nerve pathology and guide surgery.

PubMed

Osorio, Joseph A; Breshears, Jonathan D; Arnaout, Omar; Simon, Neil G; Hastings-Robinson, Ashley M; Aleshi, Pedram; Kliot, Michel

2015-09-01

OBJECT The objective of this study was to provide a technique that could be used in the preoperative period to facilitate the surgical exploration of peripheral nerve pathology. METHODS The authors describe a technique in which 1) ultrasonography is used in the immediate preoperative period to identify target peripheral nerves, 2) an ultrasound-guided needle electrode is used to stimulate peripheral nerves to confirm their position, and then 3) a methylene blue (MB) injection is performed to mark the peripheral nerve pathology to facilitate surgical exploration. RESULTS A cohort of 13 patients with varying indications for peripheral nerve surgery is presented in which ultrasound guidance, stimulation, and MB were used to localize and create a road map for surgeries. CONCLUSIONS Preoperative ultrasound-guided MB administration is a promising technique that peripheral nerve surgeons could use to plan and execute surgery.

Acceleration of Regeneration of Large-Gap Peripheral Nerve Injuries Using Acellular Nerve Allografts Plus Amniotic Fluid Derived Stem Cells (AFS)

DTIC Science & Technology

2017-09-01

AFS seeded ANA used for nerve repair resulted in an improved functional outcome for the rats compared to ANA alone and were equivalent to those...junction morphology were equivalent between the AFS seeded ANA. Additional studies investigated the use of post-partum acellular materials to promote...techniques for repairing large-gap (6 cm) nerve injuries in non -human primates. This pre-clinical model represents a more translational model of peripheral

Recombinant human antibody fragment against tetanus toxoid produced by phage display.

PubMed

Neelakantam, B; Sridevi, N V; Shukra, A M; Sugumar, P; Samuel, S; Rajendra, L

2014-03-01

Phage display technology is a powerful in vitro method for the identification of specific monoclonal antibodies (antibody fragments) to an antigenic target and allows the rapid generation and selection of high affinity, fully human antibodies directed toward any disease target appropriate for antibody therapy. In the present study, we exploited the phage display technology for the selection of an antigen binding fragment (Fabs) toward tetanus toxoid using human naïve phage antibody library constructed from peripheral blood lymphocytes of naïve human donors. The phages displaying Fab were subjected to three rounds of bio-panning with tetanus toxoid as antigen on a solid phase. The high affinity antibody fragments were expressed in HB2151 strain of Escherichia coli and purified by immobilized metal affinity chromatography. The binding activity and specificity of the antibody fragment was established by its reactivity toward tetanus toxoid and non-reactivity toward other related toxins as determined by enzyme-linked immunosorbent assay and immunoblot analysis. The selected Fab fragment forming the antigen-binding complexes with the toxoid in flocculation assay indicates that the Fab may have a potential neutralizing ability toward antigen.

Human fascioliasis with biliary complications.

PubMed

Kumari, V; Banerjee, Tuhina; Negi, N; Gupta, M I; Tiwari, K; Gupta, M

2013-01-01

We report a case of human fascioliasis adding to the few of the previously reported cases in India. A young boy from rural background in Bihar presented with diarrhea, vomiting, hepatic tenderness, jaundice and fever along with peripheral eosinophilia. Examination of stool revealed yellow-brown eggs of Fasciola hepatica. Human fascioliasis should be kept in mind in patients with cholangitis and eosinophilia especially in areas of sporadic occurrence.

Virtual Reality as a Distraction Technique in Chronic Pain Patients

PubMed Central

Gao, Kenneth; Sulea, Camelia; Wiederhold, Mark D.

2014-01-01

Abstract We explored the use of virtual reality distraction techniques for use as adjunctive therapy to treat chronic pain. Virtual environments were specifically created to provide pleasant and engaging experiences where patients navigated on their own through rich and varied simulated worlds. Real-time physiological monitoring was used as a guide to determine the effectiveness and sustainability of this intervention. Human factors studies showed that virtual navigation is a safe and effective method for use with chronic pain patients. Chronic pain patients demonstrated significant relief in subjective ratings of pain that corresponded to objective measurements in peripheral, noninvasive physiological measures. PMID:24892196

Myelomonocytic THP-1 cells for in vitro testing of immunomodulatory properties of nanoparticles.

PubMed

Schroecksnadel, Sebastian; Jenny, Marcel; Fuchs, Dietmar

2011-02-01

The use of nanoparticles for new therapeutic and diagnostics options represents a new risk for individuals exposed to such compounds. The myelomonocytic cell line THP-1 could be a useful alternative to human peripheral blood mononuclear cells (PBMC) to test for effects of drugs and compounds. Stimulation degree of cells can be monitored by measurement of neopterin and/or the kynurenine to tryptophan ratio. The method is robust and reproducible in the range of 0.1-1.0 microg/ml of LPS. However, compared to the PBMC assay it will not reveal any effect on the T-cell interaction.

Action of the photosensitizer QLT0074 upon human T lymphocytes in vitro

NASA Astrophysics Data System (ADS)

Hunt, David W. C.; Jiang, Huijun; Salmon, Ruth A.; Granville, David J.; North, John R.; Richter, Anna M.

2001-04-01

A new photosensitizer, presently designated QLT0074, may be useful for the treatment of skin conditions, particularly those mediated by T lymphocytes, with photodynamic therapy (PDT). QLT0074 was tested against human peripheral blood T cells and Jurkat T lymphoma cells. Low concentrations of QLT0074 and blue light were sufficient to induce apoptosis in peripheral blood T cells or Jurkat T lymphoma cells as indicated by expression of the apoptosis-associated mitochondrial 7A6 marker, annexin-V labeling or activation of capsase-3 and cleavage of the capsase substrate poly(ADP-ribose)polymerase (PARP). Flow cytometry studies performed following PDT showed that peripheral blood T cells with high expression of the interleukin-2 receptor (CD25) took up greater amounts of QLT0074 and were eliminated to a greater degree than T cells with low CD25 levels. This effect of PDT was also shown by the reduction in the percentage of T cells that expressed other activation-associated markers such as very late activation antigen-4 (CD49d), human leukocyte antigen DR (HLA-DR), intercellular adhesion molecule-1 (CD54) and Fas (CD95). In the case of T cells that remained viable following PDT, CD25 expression was lower while CD54, CD95 and HLA-DR levels were unchanged. Thus, PDT with QLT0074 has selective, dose-dependent effects on T cells in vitro.

Examining FKBP5 mRNA expression in human iPSC-derived neural cells

PubMed Central

Lieberman, Richard; Kranzler, Henry R.; Levine, Eric S.; Covault, Jonathan

2016-01-01

In peripheral blood leukocytes, FKBP5 mRNA expression is upregulated following glucocorticoid receptor activation. The single nucleotide polymorphism rs1360780 in FKBP5 is associated with psychiatric illness and has functional molecular effects. However, examination of FKBP5 regulation has largely been limited to peripheral cells, which may not reflect regulation in neural cells. We used 27 human induced pluripotent stem cell lines (iPSCs) derived from 20 subjects to examine FKBP5 mRNA expression following GR activation. Following differentiation into forebrain-lineage neural cultures, cells were exposed to 1μM dexamethasone and mRNA expression of FKBP5 and NR3C1 analyzed. Results from the iPSC-derived neural cells were compared with those from 15 donor matched fibroblast lines. Following dexamethasone treatment, there was a 670% increase in FKBP5 expression in fibroblasts, mimicking findings in peripheral blood-derived cells, but only a 23% increase in iPSC-derived neural cultures. FKBP5 rs1360780 genotype did not affect the induction of FKBP5 mRNA in either fibroblasts or neural cells. These results suggest that iPSC-derived forebrain-lineage neurons may not be an optimal neural cell type in which to examine relationships between GR activation, FKBP5 expression, and genetic variation in human subjects. Further, FKBP5 induction following GR activation may differ between cell types derived from the same individual. PMID:27915167

Multipotent progenitor cells are present in human peripheral blood.

PubMed

Cesselli, Daniela; Beltrami, Antonio Paolo; Rigo, Silvia; Bergamin, Natascha; D'Aurizio, Federica; Verardo, Roberto; Piazza, Silvano; Klaric, Enio; Fanin, Renato; Toffoletto, Barbara; Marzinotto, Stefania; Mariuzzi, Laura; Finato, Nicoletta; Pandolfi, Maura; Leri, Annarosa; Schneider, Claudio; Beltrami, Carlo Alberto; Anversa, Piero

2009-05-22

To determine whether the peripheral blood in humans contains a population of multipotent progenitor cells (MPCs), products of leukapheresis were obtained from healthy donor volunteers following the administration of granulocyte colony-stimulating factor. Small clusters of adherent proliferating cells were collected, and these cells continued to divide up to 40 population doublings without reaching replicative senescence and growth arrest. MPCs were positive for the transcription factors Nanog, Oct3/4, Sox2, c-Myc, and Klf4 and expressed several antigens characteristic of mesenchymal stem cells. However, they were negative for markers of hematopoietic stem/progenitor cells and bone marrow cell lineages. MPCs had a cloning efficiency of approximately 3%, and following their expansion, retained a highly immature phenotype. Under permissive culture conditions, MPCs differentiated into neurons, glial cells, hepatocytes, cardiomyocytes, endothelial cells, and osteoblasts. Moreover, the gene expression profile of MPCs partially overlapped with that of neural and embryonic stem cells, further demonstrating their primitive, uncommitted phenotype. Following subcutaneous transplantation in nonimmunosuppressed mice, MPCs migrated to distant organs and integrated structurally and functionally within the new tissue, acquiring the identity of resident parenchymal cells. In conclusion, undifferentiated cells with properties of embryonic stem cells can be isolated and expanded from human peripheral blood after granulocyte colony-stimulating factor administration. This cell pool may constitute a unique source of autologous cells with critical clinical import.

Genoprotective properties of astaxanthin revealed by ionizing radiation exposure in vitro on human peripheral blood lymphocytes.

PubMed

Pilinska, M A; Кurinnyi, D A; Rushkovsky, S R; Dybska, O B

2016-12-01

to identify possible radioprotective properties of astaxanthin by means of cytogenetic criteria. Cultivation of peripheral blood lymphocytes from five apparently healthy volunteers; treatment of lym phocytes' cultures by astaxanthin in final concentrations 20 μg/ml in Go phase of mitotic cycle, prior to ? irradia tion in vitro in a dose 1 Gy; cytogenetic analysis the uniformly stained slides of metaphase chromosomes. The elec trophoresis of individual cells (Comet assay); visualization of results under fluorescent microscope; accounting the number of nucleoid the fourth grade that correspond to apoptosis of the cells. Established that astaxanthin in final concentration 20.0 μg/ml exposed to the culture of human peripher al blood lymphocytes in the early G0 phase of mitotic cycle leads to significant reduction of cytogenetic effects induced by gamma irradiation in vitro in dose 1.0 Gy (from 26.05 ± 1.81 to 9.08 ± 0.78 per 100 cells, respectively) and to significant increase the frequency of apoptotic cells at the 48 hour of cultivation (from (3.78 ± 0.24) to (8.26 ± 0.91) %, respectively). The results obtained show the ability of astaxanthin to considerable weakening of radioinduced muta genic effect in human peripheral blood lymphocytes, which testify its powerful radioprotective potential. M. А. Pilinska, D. А. Кurinnyi, S. R. Rushkovsky, О. B. Dybska.

Sensory neuropathy may cause central neuronal reorganization but does not respecify perceptual quality or localization of sensation.

PubMed

Ginanneschi, Federica; Mondelli, Mauro; Rossi, Alessandro

2012-10-01

Functional reorganization in the somatosensory network after peripheral nerve lesions has been suspected to modify the clinical expression of symptoms. However, no conclusive evidence exists to support this notion. We addressed this question by investigating the topographic distribution of the subjective sensory report in various chronic human mononeuropathies. We report the clinical results of 86 patients who were diagnosed with meralgia paresthetica, 86 patients with ulnar neuropathy at the elbow, and 203 patients with carpal tunnel syndrome. In the carpal tunnel syndrome group, 10% of the patients exhibited a spread of sensory symptoms beyond the innervation territory of the median nerve. As previously reported, this spread was contingent upon an indirect compressive lesion of the ulnar nerve at the wrist. In all of the patients who were affected with meralgia paresthetica or ulnar neuropathy at the elbow, the peripheral referral of sensation was always within the anatomic distribution of the affected nerve. In human neuropathies, the projected sensory symptoms are restricted to the innervation territories of the affected nerves, with no extraterritorial spread. Thus, the somatosensory localization function remains accurate, despite the central reorganization that presumably occurs after nerve injury. We conclude that reorganization of the sensory connections within the central nervous system after peripheral nerve injury in humans is a clinically silent adaptive phenomenon.

Neutrophilic respiratory tract inflammation and peripheral blood neutrophilia after grain sorghum dust extract challenge.

PubMed

Von Essen, S G; O'Neill, D P; McGranaghan, S; Olenchock, S A; Rennard, S I

1995-11-01

To determine if inhalation of grain sorghum dust in the laboratory would cause neutrophilic upper and lower respiratory tract inflammation in human volunteers, as well as systemic signs of illness. Prospective. University of Nebraska Medical Center. Thirty normal volunteers. Inhalation challenge with 20 mL of a nebulized solution of filter-sterilized grain sorghum dust extract (GSDE). One group received prednisone, 20 mg for 2 days, prior to the challenge. Bronchoscopy with bronchoalveolar lavage (BAL) was performed 24 h after challenge, with samples collected as bronchial and alveolar fractions. Findings included visible signs of airways inflammation, quantified as the bronchitis index. The percentage of bronchial neutrophils was significantly increased in those challenged with GSDE vs the control solution, Hanks' balanced salt solution (40.3 +/- 4.5% vs 14.3 +/- 5.1%, p < or = .01). Similar findings were seen in the alveolar fraction. Pretreatment with corticosteroids did not prevent the rise in neutrophils recovered by BAL. Peripheral blood neutrophils were also increased in volunteers challenged with the grain dust extract. To explain the increase in peripheral blood neutrophil counts, the capacity of the peripheral blood neutrophils to migrate in chemotaxis experiments was examined. The results demonstrate an increase in peripheral blood neutrophils and an increase in chemotactic responsiveness. Inhalation challenge with a grain dust extract causes respiratory tract inflammation and a peripheral blood neutrophilia. One reason for this may be an increase in activated peripheral blood neutrophils.

Regulated expression of telomerase activity in human T lymphocyte development and activation

PubMed Central

1996-01-01

Telomerase, a ribonucleoprotein that is capable of synthesizing telomeric repeats, is expressed in germline and malignant cells, and is absent in most normal human somatic cells. The selective expression of telomerase has thus been proposed to be a basis for the immortality of the germline and of malignant cells. In the present study, telomerase activity was analyzed in normal human T lymphocytes. It was found that telomerase is expressed at a high level in thymocyte subpopulations, at an intermediate level in tonsil T lymphocytes, and at a low to undetectable level in peripheral blood T lymphocytes. Moreover, telomerase activity is highly inducible in peripheral T lymphocytes by activation through CD3 with or without CD28 costimulation, or by stimulation with phorbol myristate acetate (PMA)/ionomycin. The induction of telomerase by anti-CD3 plus anti-CD28 (anti-CD3/CD28) stimulation required RNA and protein synthesis, and was blocked by herbimycin A, an inhibitor of S pi protein tyrosine kinases. The immunosuppressive drug cyclosporin A selectively inhibited telomerase induction by PMA/ionomycin and by anti-CD3, but not by anti-CD3/CD28. Although telomerase activity in peripheral T lymphocytes was activation dependent and correlated with cell proliferation, it was not cell cycle phase restricted. These results indicate that the expression of telomerase in normal human T lymphocytes is both developmentally regulated and activation induced. Telomerase may thus play a permissive role in T cell development and in determining the capacity of lymphoid cells for cell division and clonal expansion. PMID:8676067

Transcription factor fos-related antigen-2 induces progressive peripheral vasculopathy in mice closely resembling human systemic sclerosis.

PubMed

Maurer, Britta; Busch, Nicole; Jüngel, Astrid; Pileckyte, Margarita; Gay, Renate E; Michel, Beat A; Schett, Georg; Gay, Steffen; Distler, Jörg; Distler, Oliver

2009-12-08

Microvascular damage is one of the first pathological changes in systemic sclerosis. In this study, we investigated the role of Fos-related antigen-2 (Fra-2), a transcription factor of the activator protein-1 family, in the peripheral vasculopathy of systemic sclerosis and examined the underlying mechanisms. Expression of Fra-2 protein was significantly increased in skin biopsies of systemic sclerosis patients compared with healthy controls, especially in endothelial and vascular smooth muscle cells. Fra-2 transgenic mice developed a severe loss of small blood vessels in the skin that was paralleled by progressive skin fibrosis at 12 weeks of age. The reduction in capillary density was preceded by a significant increase in apoptosis in endothelial cells at week 9 as detected by immunohistochemistry. Similarly, suppression of Fra-2 by small interfering RNA prevented human microvascular endothelial cells from staurosporine-induced apoptosis and improved both the number of tubes and the cumulative tube lengths in the tube formation assay. In addition, cell migration in the scratch assay and vascular endothelial growth factor-dependent chemotaxis in a modified Boyden chamber assay were increased after transfection of human microvascular endothelial cells with Fra-2 small interfering RNA, whereas proliferation was not affected. Fra-2 is present in human systemic sclerosis and may contribute to the development of microvasculopathy by inducing endothelial cell apoptosis and by reducing endothelial cell migration and chemotaxis. Fra-2 transgenic mice are a promising preclinical model to study the mechanisms and therapeutic approaches of the peripheral vasculopathy in systemic sclerosis.

Effect of β-agonist on the dexamethasone-induced expression of aromatase by the human monocyte cells

PubMed Central

Ohno, Shuji; Wachi, Hiroshi

2017-01-01

Emerging evidence suggests that sex steroids are important for human skin health. In particular, estrogen improves skin thickness, elasticity and moisture of older women. The major source of circulating estrogen is the ovary; however, local estrogen synthesis and secretion have important roles in, for example, bone metabolism and breast cancer development. We hypothesized that infiltrated peripheral monocytes are one of the sources of estrogen in skin tissues. We also hypothesized that, during atopic dermatitis under stress, a decline in the hypothalamus–pituitary–adrenal axis (HPA) and facilitation of the (hypothalamus)–sympathetic–adrenomedullary system (SAM) attenuates estrogen secretion from monocytes. Based on this hypothesis, we tested aromatase expression in the human peripheral monocyte-derived cell line THP-1 in response to the synthetic glucocorticoid dexamethasone (Dex), the synthetic β-agonist isoproterenol (Iso) and the β-antagonist propranolol (Pro). Dex mimics glucocorticoid secreted during excitation of the HPA, and Iso mimics catecholamine secreted during excitation of the SAM. We found that aromatase activity and the CYP19A1 gene transcript were both upregulated in THP-1 cells in the presence of Dex. Addition of Iso induced their downregulation and further addition of Pro rescued aromatase expression. These results may suggest that attenuation of estrogen secretion from peripheral monocytes could be a part of the pathology of stress-caused deterioration of atopic dermatitis. Further examination using an in vitro human skin model including THP-1 cells might be a valuable tool for investigating the therapeutic efficacy and mechanism of estrogen treatment for skin health. PMID:28126832

Effect of β-agonist on the dexamethasone-induced expression of aromatase by the human monocyte cells.

PubMed

Watanabe, Masatada; Ohno, Shuji; Wachi, Hiroshi

2017-02-01

Emerging evidence suggests that sex steroids are important for human skin health. In particular, estrogen improves skin thickness, elasticity and moisture of older women. The major source of circulating estrogen is the ovary; however, local estrogen synthesis and secretion have important roles in, for example, bone metabolism and breast cancer development. We hypothesized that infiltrated peripheral monocytes are one of the sources of estrogen in skin tissues. We also hypothesized that, during atopic dermatitis under stress, a decline in the hypothalamus-pituitary-adrenal axis (HPA) and facilitation of the (hypothalamus)-sympathetic-adrenomedullary system (SAM) attenuates estrogen secretion from monocytes. Based on this hypothesis, we tested aromatase expression in the human peripheral monocyte-derived cell line THP-1 in response to the synthetic glucocorticoid dexamethasone (Dex), the synthetic β-agonist isoproterenol (Iso) and the β-antagonist propranolol (Pro). Dex mimics glucocorticoid secreted during excitation of the HPA, and Iso mimics catecholamine secreted during excitation of the SAM. We found that aromatase activity and the CYP19A1 gene transcript were both upregulated in THP-1 cells in the presence of Dex. Addition of Iso induced their downregulation and further addition of Pro rescued aromatase expression. These results may suggest that attenuation of estrogen secretion from peripheral monocytes could be a part of the pathology of stress-caused deterioration of atopic dermatitis. Further examination using an in vitro human skin model including THP-1 cells might be a valuable tool for investigating the therapeutic efficacy and mechanism of estrogen treatment for skin health. © 2017 The authors.

GARP inhibits allergic airway inflammation in a humanized mouse model.

PubMed

Meyer-Martin, H; Hahn, S A; Beckert, H; Belz, C; Heinz, A; Jonuleit, H; Becker, C; Taube, C; Korn, S; Buhl, R; Reuter, S; Tuettenberg, A

2016-09-01

Regulatory T cells (Treg) represent a promising target for novel treatment strategies in patients with inflammatory/allergic diseases. A soluble derivate of the Treg surface molecule glycoprotein A repetitions predominant (sGARP) has strong anti-inflammatory and regulatory effects on human cells in vitro as well as in vivo through de novo induction of peripheral Treg. The aim of this study was to investigate the immunomodulatory function of sGARP and its possible role as a new therapeutic option in allergic diseases using a humanized mouse model. To analyze the therapeutic effects of sGARP, adult NOD/Scidγc(-/-) (NSG) mice received peripheral blood mononuclear cells (PBMC) derived from allergic patients with sensitization against birch allergen. Subsequently, allergic inflammation was induced in the presence of Treg alone or in combination with sGARP. In comparison with mice that received Treg alone, additional treatment with sGARP reduced airway hyperresponsiveness (AHR), influx of neutrophils and macrophages into the bronchoalveolar lavage (BAL), and human CD45(+) cells in the lungs. Furthermore, the numbers of mucus-producing goblet cells and inflammatory cell infiltrates were reduced. To elucidate whether the mechanism of action of sGARP involves the TGF-β receptor pathway, mice additionally received anti-TGF-β receptor II (TGF-βRII) antibodies. Blocking the signaling of TGF-β through TGF-βRII abrogated the anti-inflammatory effects of sGARP, confirming its essential role in inhibiting the allergic inflammation. Induction of peripheral tolerance via sGARP is a promising potential approach to treat allergic airway diseases. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Associations between parenting behavior and anxiety in a rodent model and a clinical sample: relationship to peripheral BDNF levels

PubMed Central

Dalle Molle, R; Portella, A K; Goldani, M Z; Kapczinski, F P; Leistner-Segala, S; Salum, G A; Manfro, G G; Silveira, P P

2012-01-01

Adverse early-life environment is associated with anxiety-like behaviors and disorders. Brain-derived neurotrophic factor (BDNF) is sensitive to this environment and could be a marker of underlying brain changes. We aimed at evaluating the development of anxiety-like behaviors in a rat model of early adversity, as well as the possible association with BDNF levels. Similar associations were investigated in a sample of adolescent humans. For the rat study, Wistar rat litters were divided into: early-life stress (ELS, limited access to nesting material) and control groups. Maternal behavior was observed from days 1 to 9 of life and, as adults, rats were subjected to behavioral testing and BDNF measurements in plasma, hippocampus, amygdala and periaqueductal gray. For the human study, 129 adolescents were evaluated for anxiety symptoms and perceived parental care. Serum BDNF levels and the Val66Met polymorphism of the BDNF gene were investigated. We found that ELS dams showed more pure contact, that is, contact with low care and high control, toward pups, and their adult offspring demonstrated higher anxiety-like behaviors and plasma BDNF. Also the pure contact correlated positively with adult peripheral BDNF. Similarly in humans, there was a positive correlation between maternal overprotection and serum BDNF only in Met carriers. We also found negative correlations between maternal warmth and separation anxiety, social phobia and school phobia. Finally, our translational approach revealed that ELS, mediated through variations in maternal care, is associated with anxiety in both rats and humans and increased peripheral BDNF may be marking these phenomena. PMID:23168995

Decreased human leukocyte antigen A*02:01 frequency is associated with risk of glioma and existence of human cytomegalovirus: a case-control study in Northern China.

PubMed

Han, Sheng; Deng, Jian; Wang, Zixun; Liu, Huan; Cheng, Wen; Wu, Anhua

2017-10-01

Human leukocyte antigens (HLAs) play an important role in host defense against viral infection and tumorigenesis. Human cytomegalovirus (HCMV) has been linked to glioma development. This study investigated the relationship between HLA distribution, presence of HCMV, and glioma development in a Han Chinese population. The study population included 150 glioma patients and 150 tumor-free brain injury control subjects (control-A) matched according to geography, ethnicity, age, and gender. HLA allele frequency was compared between the two groups using peripheral blood samples by PCR sequence-based typing. These data were also compared with HLA frequencies obtained from a Northern Chinese Han population database (control-B). HCMV DNA was detected in the peripheral blood of glioma patients and control group-A by nested PCR. The expression of HCMV proteins IE1-72 and pp65 in tumor tissues was evaluated by immunohistochemistry. The frequency of HLA-A*02:01 was decreased in glioma patients as compared to control group-A and -B (P < 0.001 and P = 0.001, respectively). The age/sex-adjusted odds ratio for HLA-A*02:01 positivity vs. negativity was 0.392 (95% confidence interval 0.225-0.683). HCMV was more frequently detected in the peripheral blood and tumor tissue of HLA-A*02:01-negative glioma patients. HLA-A*02:01 and HCMV were not associated with overall survival. There is a correlation between decreased HLA-A*0201 allele frequency and glioma susceptibility.

Kidins220/ARMS depletion is associated with the neural-to Schwann-like transition in a human neuroblastoma cell line model.

PubMed

Rogers, Danny A; Schor, Nina F

2013-03-10

Peripheral neuroblastic tumors exist as a heterogeneous mixture of neuroblastic (N-type) cells and Schwannian stromal (S-type) cells. These stromal cells not only represent a differentiated and less aggressive fraction of the tumor, but also have properties that can influence the further differentiation of nearby malignant cells. In vitro neuroblastoma cultures exhibit similar heterogeneity with N-type and S-type cells representing the neuroblastic and stromal portions of the tumor, respectively, in behavior, morphology, and molecular expression patterns. In this study, we deplete kinase D-interacting substrate of 220kD (Kidins220) with an shRNA construct and thereby cause morphologic transition of the human SH-SY5Y neuroblastoma cell line from N-type to S-type. The resulting cells have similar morphology and expression profile to SH-EP1 cells, a native S-type cell line from the same parent cell line, and to SH-SY5Y cells treated with BrdU, a treatment that induces S-type morphology. Specifically, both Kidins220-deficient SH-SY5Y cells and native SH-EP1 cells demonstrate down-regulation of the genes DCX and STMN2, markers for the neuronal lineage. We further show that Kidins220, DCX and STMN2 are co-down-regulated in cells of S-type morphology generated by methods other than Kidins220 depletion. Finally, we report that the association of low Kidins220 expression with S-type morphology and low DCX and STMN2 expression is demonstrated in spontaneously occurring human peripheral neuroblastic tumors. We propose that Kidins220 is critical in N- to S-type transition of neural crest tumor cells. Copyright © 2013 Elsevier Inc. All rights reserved.

The Brain Response to Peripheral Insulin Declines with Age: A Contribution of the Blood-Brain Barrier?

PubMed Central

Heni, Martin; Maetzler, Walter; Fritsche, Andreas; Häring, Hans-Ulrich; Hennige, Anita M.

2015-01-01

Objectives It is a matter of debate whether impaired insulin action originates from a defect at the neural level or impaired transport of the hormone into the brain. In this study, we aimed to investigate the effect of aging on insulin concentrations in the periphery and the central nervous system as well as its impact on insulin-dependent brain activity. Methods Insulin, glucose and albumin concentrations were determined in 160 paired human serum and cerebrospinal fluid (CSF) samples. Additionally, insulin was applied in young and aged mice by subcutaneous injection or intracerebroventricularly to circumvent the blood-brain barrier. Insulin action and cortical activity were assessed by Western blotting and electrocorticography radiotelemetric measurements. Results In humans, CSF glucose and insulin concentrations were tightly correlated with the respective serum/plasma concentrations. The CSF/serum ratio for insulin was reduced in older subjects while the CSF/serum ratio for albumin increased with age like for most other proteins. Western blot analysis in murine whole brain lysates revealed impaired phosphorylation of AKT (P-AKT) in aged mice following peripheral insulin stimulation whereas P-AKT was comparable to levels in young mice after intracerebroventricular insulin application. As readout for insulin action in the brain, insulin-mediated cortical brain activity instantly increased in young mice subcutaneously injected with insulin but was significantly reduced and delayed in aged mice during the treatment period. When insulin was applied intracerebroventricularly into aged animals, brain activity was readily improved. Conclusions This study discloses age-dependent changes in insulin CSF/serum ratios in humans. In the elderly, cerebral insulin resistance might be partially attributed to an impaired transport of insulin into the central nervous system. PMID:25965336

Role of trophic factors GDNF, IGF-1 and VEGF in major depressive disorder: A comprehensive review of human studies

PubMed Central

Sharma, Ajaykumar N.; da Costa e Silva, Bruno Fernando Borges; Soares, Jair C.; Carvalho, André F.; Quevedo, Joao

2016-01-01

Rationale The neurotrophin hypothesis of major depressive disorder (MDD) postulates that this illness results from aberrant neurogenesis in brain regions that regulates emotion and memory. Notwithstanding this theory has primarily implicated BDNF in the neurobiology of MDD. Recent evidence suggests that other trophic factors namely GDNF, VEGF and IGF-1 may also be involved. Purpose The present review aimed to critically summarize evidence regarding changes in GDNF, IGF-1 and VEGF in individuals with MDD compared to healthy controls. In addition, we also evaluated the role of these mediators as potential treatment response biomarkers for MDD. Methods A comprehensive review of original studies studies measuring peripheral, central or mRNA levels of GDNF, IGF-1 or VEGF in patients with MDD was conducted. The PubMed/MEDLINE database was searched for peer-reviewed studies published in English through June 2nd, 2015. Results Most studies reported a reduction in peripheral GDNF and its mRNA levels in MDD patients versus controls. In contrast, IGF-1 levels in MDD patients compared to controls were discrepant across studies. Finally, most studies reported high peripheral VEGF levels and mRNA expression in MDD patients compared to healthy controls. Conclusions GDNF, IGF-1 and VEGF levels and their mRNA expression appear to be differentially altered in MDD patients compared to healthy individuals, indicating that these molecules might play an important role in the pathophysiology of depression and antidepressant action of therapeutic interventions. PMID:26956384

Challenges Evaluating Chemotherapy-Induced Peripheral Neuropathy in Childhood Cancer Survivors.

PubMed

Mohrmann, Caroline; Armer, Jane; Hayashi, Robert J

Children treated for cancer are exposed to a variety of chemotherapeutic agents with known toxicity to the peripheral nervous system. The side effect of peripheral neuropathy can cause changes in sensation, function, and even cause pain. Although peripheral neuropathy is recognized by pediatric oncology nurses as an important and significant side effect, measuring neuropathy can be quite complex for clinical care and research efforts. With more children surviving a cancer diagnosis today, this issue is increasingly important for childhood cancer survivors. This article has reviewed existing literature examining peripheral neuropathy in childhood cancer survivors with particular interest paid to measurement tools available and needs for future research. It is important for nurses to choose appropriate measures for clinical care and research methods in order to have an impact on patients experiencing this condition.

Advances and Future Applications of Augmented Peripheral Nerve Regeneration

PubMed Central

Jones, Salazar; Eisenberg, Howard M.; Jia, Xiaofeng

2016-01-01

Peripheral nerve injuries remain a significant source of long lasting morbidity, disability, and economic costs. Much research continues to be performed in areas related to improving the surgical outcomes of peripheral nerve repair. In this review, the physiology of peripheral nerve regeneration and the multitude of efforts to improve surgical outcomes are discussed. Improvements in tissue engineering that have allowed for the use of synthetic conduits seeded with neurotrophic factors are highlighted. Selected pre-clinical and available clinical data using cell based methods such as Schwann cell, undifferentiated, and differentiated stem cell transplantation to guide and enhance peripheral nerve regeneration are presented. The limitations that still exist in the utility of neurotrophic factors and cell-based therapies are outlined. Strategies that are most promising for translation into the clinical arena are suggested. PMID:27618010

EFFECT OF RESIDUAL SPLENIC FUNCTION AND FOLATE LEVELS ON THE FREQUENCY OF MICRONUCLEATED RED BLOOD CELLS IN SPLENECTOMIZED HUMANS

EPA Science Inventory

Rates of micronucleated erythrocytes in the peripheral blood of splenectomized individuals can be used as an index of genetic damage to erythrocyte recursor cells in the bone marrow. his is in contrast to non-splenectomized humans, whose micronucleated erythrocytes are removed by...

Interaction of bovine peripheral blood polymorphonuclear cells and Leptospira species; innate responses in the natural bovine reservoir host.

USDA-ARS?s Scientific Manuscript database

Cattle are the reservoir hosts of Leptospira borgpetersenii serovar Hardjo, and also be reservoir hosts of other Leptospira species such as L. kirschneri, and L. interrogans. As a reservoir host, cattle shed Leptospira, infecting other animals, including humans. Previous studies with human and murin...

Hemagglutination and graft-versus-host disease in the severe combined immunodeficiency mouse lymphoproliferative disease model.

PubMed Central

Pirruccello, S. J.; Nakamine, H.; Beisel, K. W.; Kleveland, K. L.; Okano, M.; Taguchi, Y.; Davis, J. R.; Mahloch, M. L.; Purtilo, D. T.

1992-01-01

In the course of evaluating the severe combined immunodeficiency mouse-human peripheral blood lymphocyte (SCID-PBL) model of lymphoproliferative disease, we noted hemagglutination occurring in peripheral blood smears of mice with serum human immunoglobulin levels greater than 1.0 mg/ml. The hemagglutinating process was mediated by human anti-mouse red cell antibodies of the IgM class, peaked at five to seven weeks post-transfer of 5 to 7 x 10(7) human PBL and was generally self limiting. However, death resulted in some mice when serum immunoglobulin levels were greater than 3.0 mg/ml. The most severely affected mice had hemagglutination induced congestion of liver, lungs and spleen. Several mice also had lesions consistent with graft-versus-host disease (GVHD) including focal hepatic necrosis and destruction of mouse splenic hematopoietic elements. The lesions associated with hemagglutination and GVHD in SCID-PBL mice are distinct from those associated with EBV-induced lymphoproliferation. Recognition of these pathologic processes are required for a thorough understanding of the SCID-PBL model. Images Figure 1 Figure 3 Figure 4 PMID:1580330

Betaine:homocysteine methyltransferase--a new assay for the liver enzyme and its absence from human skin fibroblasts and peripheral blood lymphocytes.

PubMed

Wang, J A; Dudman, N P; Lynch, J; Wilcken, D E

1991-12-31

Chronic elevation of plasma homocysteine is associated with increased atherogenesis and thrombosis, and can be lowered by betaine (N,N,N-trimethylglycine) treatment which is thought to stimulate activity of the enzyme betaine:homocysteine methyltransferase. We have developed a new assay for this enzyme, in which the products of the enzyme-catalysed reaction between betaine and homocysteine are oxidised by performic acid before being separated and quantified by amino acid analysis. This assay confirmed that human liver contains abundant betaine:homocysteine methyltransferase (33.4 nmol/h/mg protein at 37 degrees C, pH 7.4). Chicken and lamb livers also contain the enzyme, with respective activities of 50.4 and 6.2 nmol/h/mg protein. However, phytohaemagglutinin-stimulated human peripheral blood lymphocytes and cultured human skin fibroblasts contained no detectable betaine:homocysteine methyltransferase (less than 1.4 nmol/h/mg protein), even after cells were pre-cultured in media designed to stimulate production of the enzyme. The results emphasize the importance of the liver in mediating the lowering of elevated circulating homocysteine by betaine.

Chloride channel blockers promote relaxation of TEA-induced contraction in airway smooth muscle.

PubMed

Yim, Peter D; Gallos, George; Perez-Zoghbi, Jose F; Trice, Jacquelyn; Zhang, Yi; Siviski, Matthew; Sonett, Joshua; Emala, Charles W

2013-01-01

Enhanced airway smooth muscle (ASM) contraction is an important component in the pathophysiology of asthma. We have shown that ligand gated chloride channels modulate ASM contractile tone during the maintenance phase of an induced contraction, however the role of chloride flux in depolarization-induced contraction remains incompletely understood. To better understand the role of chloride flux under these conditions, muscle force (human ASM, guinea pig ASM), peripheral small airway luminal area (rat ASM) and airway smooth muscle plasma membrane electrical potentials (human cultured ASM) were measured. We found ex vivo guinea pig airway rings, human ASM strips and small peripheral airways in rat lungs slices relaxed in response to niflumic acid following depolarization-induced contraction induced by K(+) channel blockade with tetraethylammonium chloride (TEA). In isolated human airway smooth muscle cells TEA induce depolarization as measured by a fluorescent indicator or whole cell patch clamp and this depolarization was reversed by niflumic acid. These findings demonstrate that ASM depolarization induced contraction is dependent on chloride channel activity. Targeting of chloride channels may be a novel approach to relax hypercontractile airway smooth muscle in bronchoconstrictive disorders.

Prostaglandin E2 suppresses beta1-integrin expression via E-prostanoid receptor in human monocytes/macrophages.

PubMed

Hasegawa, Shunji; Ichiyama, Takashi; Kohno, Fumitaka; Korenaga, Yuno; Ohsaki, Ayami; Hirano, Reiji; Haneda, Yasuhiro; Fukano, Reiji; Furukawa, Susumu

2010-01-01

Beta1-integrins mediate cell attachment to different extracellular matrix proteins, intracellular proteins, and intercellular adhesions. Recently, it has been reported that prostaglandin E2 (PGE2) has anti-inflammatory properties such as inhibition of the expression of adhesion molecules or production of chemokines. However, the effect of PGE2 on the expression of beta1-integrin remains unknown. In this study, we investigated the effects of PGE2 on the expression of beta1-integrin in the human monocytic cell line THP-1 and in CD14+ monocytes/macrophages in human peripheral blood. For this, we examined the role of four subtypes of PGE2 receptors and E-prostanoid (EP) receptors on PGE2-mediated inhibition. We found that PGE2 significantly inhibited the expression of beta1-integrin, mainly through EP4 receptors in THP-1 cells and CD14+ monocytes/macrophages in human peripheral blood. We suggest that PGE2 has anti-inflammatory effects, leading to the inhibited expression of beta1-integrin in human monocytes/macrophages, and that the EP4 receptor may play an important role in PGE2-mediated inhibition. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Practical Murine Hematopathology: A Comparative Review and Implications for Research

PubMed Central

O'Connell, Karyn E; Mikkola, Amy M; Stepanek, Aaron M; Vernet, Andyna; Hall, Christopher D; Sun, Chia C; Yildirim, Eda; Staropoli, John F; Lee, Jeannie T; Brown, Diane E

2015-01-01

Hematologic parameters are important markers of disease in human and veterinary medicine. Biomedical research has benefited from mouse models that recapitulate such disease, thus expanding knowledge of pathogenetic mechanisms and investigative therapies that translate across species. Mice in health have many notable hematologic differences from humans and other veterinary species, including smaller erythrocytes, higher percentage of circulating reticulocytes or polychromasia, lower peripheral blood neutrophil and higher peripheral blood and bone marrow lymphocyte percentages, variable leukocyte morphologies, physiologic splenic hematopoiesis and iron storage, and more numerous and shorter-lived erythrocytes and platelets. For accurate and complete hematologic analyses of disease and response to investigative therapeutic interventions, these differences and the unique features of murine hematopathology must be understood. Here we review murine hematology and hematopathology for practical application to translational investigation. PMID:25926395

Physiological and pharmacologic aspects of peripheral nerve blocks

PubMed Central

Vadhanan, Prasanna; Tripaty, Debendra Kumar; Adinarayanan, S.

2015-01-01

A successful peripheral nerve block not only involves a proper technique, but also a thorough knowledge and understanding of the physiology of nerve conduction and pharmacology of local anesthetics (LAs). This article focuses on what happens after the block. Pharmacodynamics of LAs, underlying mechanisms of clinically observable phenomena such as differential blockade, tachyphylaxis, C fiber resistance, tonic and phasic blockade and effect of volume and concentration of LAs. Judicious use of additives along with LAs in peripheral nerve blocks can prolong analgesia. An entirely new group of drugs-neurotoxins has shown potential as local anesthetics. Various methods are available now to prolong the duration of peripheral nerve blocks. PMID:26330722

The Multifactorial role of Peripheral Nervous System in Bone Growth

NASA Astrophysics Data System (ADS)

Gkiatas, Ioannis; Papadopoulos, Dimitrios; Pakos, Emilios E.; Kostas-Agnantis, Ioannis; Gelalis, Ioannis; Vekris, Marios; Korompilias, Anastasios

2017-09-01

Bone alters its metabolic and anabolic activities in response to the variety of systemic and local factors such as hormones and growth factors. Classical observations describing abundance of the nerve fibers in bone also predict a paradigm that the nervous system influences bone metabolism and anabolism. Since 1916 several investigators tried to analyze the effect of peripheral nervous system in bone growth and most of them advocated for the positive effect of innervation in the bones of growing organisms. Moreover, neuronal tissue controls bone formation and remodeling. The purpose of this mini-review is to present the most recent data concerning the influence of innervation on bone growth, the current understanding of the skeletal innervation and their proposed physiological effects on bone metabolism as well as the implication of denervation in human skeletal biology in the developing organism since the peripheral neural trauma as well as peripheral neuropathies are common and they have impact on the growing skeleton.

HIV-1 Phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues

PubMed Central

Lamers, Susanna L.; Gray, Rebecca R.; Salemi, Marco; Huysentruyt, Leanne C.; McGrath, Michael

2010-01-01

Brain infection by the human immunodeficiency virus type 1 (HIV-1) has been investigated in many reports with a variety of conclusions concerning the time of entry and degree of viral compartmentalization. To address these diverse findings, we sequenced HIV-1 gp120 clones from a wide range of brain, peripheral and meningeal tissues from five patients who died from several HIV-1 associated disease pathologies. High-resolution phylogenetic analysis confirmed previous studies that showed a significant degree of compartmentalization in brain and peripheral tissue subpopulations. Some intermixing between the HIV-1 subpopulations was evident, especially in patients that died from pathologies other than HIV-associated dementia. Interestingly, the major tissue harboring virus from both the brain and peripheral tissues was the meninges. These results show that 1) HIV-1 is clearly capable of migrating out of the brain, 2) the meninges are the most likely primary transport tissues, and 3) infected brain macrophages comprise an important HIV reservoir during highly active antiretroviral therapy. PMID:21055482

Superior In vivo Transduction of Human Hepatocytes Using Engineered AAV3 Capsid.

PubMed

Vercauteren, Koen; Hoffman, Brad E; Zolotukhin, Irene; Keeler, Geoffrey D; Xiao, Jing W; Basner-Tschakarjan, Etiena; High, Katherine A; Ertl, Hildegund Cj; Rice, Charles M; Srivastava, Arun; de Jong, Ype P; Herzog, Roland W

2016-06-01

Adeno-associated viral (AAV) vectors are currently being tested in multiple clinical trials for liver-directed gene transfer to treat the bleeding disorders hemophilia A and B and metabolic disorders. The optimal viral capsid for transduction of human hepatocytes has been under active investigation, but results across various models are inconsistent. We tested in vivo transduction in "humanized" mice. Methods to quantitate percent AAV transduced human and murine hepatocytes in chimeric livers were optimized using flow cytometry and confocal microscopy with image analysis. Distinct transduction efficiencies were noted following peripheral vein administration of a self-complementary vector expressing a gfp reporter gene. An engineered AAV3 capsid with two amino acid changes, S663V+T492V (AAV3-ST), showed best efficiency for human hepatocytes (~3-times, ~8-times, and ~80-times higher than for AAV9, AAV8, and AAV5, respectively). AAV5, 8, and 9 were more efficient in transducing murine than human hepatocytes. AAV8 yielded the highest transduction rate of murine hepatocytes, which was 19-times higher than that for human hepatocytes. In summary, our data show substantial differences among AAV serotypes in transduction of human and mouse hepatocytes, are the first to report on AAV5 in humanized mice, and support the use of AAV3-based vectors for human liver gene transfer.

Transmission of molecularly undetectable circulating parasite clones leads to high infection complexity in mosquitoes post feeding.

PubMed

Grignard, Lynn; Gonçalves, Bronner P; Early, Angela M; Daniels, Rachel F; Tiono, Alfred B; Guelbéogo, Wamdaogo M; Ouédraogo, Alphonse; van Veen, Elke M; Lanke, Kjerstin; Diarra, Amidou; Nebie, Issa; Sirima, Sodiomon B; Targett, Geoff A; Volkman, Sarah K; Neafsey, Daniel E; Wirth, Dyann F; Bousema, Teun; Drakeley, Chris

2018-05-05

Plasmodium falciparum malaria infections often comprise multiple distinct parasite clones. Few datasets have directly assessed infection complexity in humans and mosquitoes they infect. Examining parasites using molecular tools may provide insights into the selective transmissibility of isolates. Using capillary electrophoresis genotyping and next generation amplicon sequencing, we analysed complexity of parasite infections in human blood and in the midguts of mosquitoes that became infected in membrane feeding experiments using the same blood material in two West African settings. Median numbers of clones in humans and mosquitoes were higher in samples from Burkina Faso (4.5, interquartile range 2-8 for humans; and 2, interquartile range 1-3 for mosquitoes) than in The Gambia (2, interquartile range 1-3 and 1, interquartile range 1-3, for humans and mosquitoes, respectively). Whilst the median number of clones was commonly higher in human blood samples, not all transmitted alleles were detectable in the human peripheral blood. In both study sample sets, additional parasite alleles were identified in mosquitoes compared with the matched human samples (10-88.9% of all clones/feeding assay, n = 73 feeding assays). The results are likely due to preferential amplification of the most abundant clones in peripheral blood but confirm the presence of low density clones that produce transmissible sexual stage parasites. Copyright © 2018. Published by Elsevier Ltd.

Evaluation of Peripheral Blood Circulation Disorder in Scleroderma Patients Using an Optical Sensor with a Pressurization Mechanism

PubMed Central

Yamakoshi, Yoshiki

2016-01-01

Blood circulation function of peripheral blood vessels in skin dermis was evaluated employing an optical sensor with a pressurization mechanism using the blood outflow and reflow characteristics. The device contains a light source and an optical sensor. When applied to the skin surface, it first exerts the primary pressure (higher than the systolic blood pressure), causing an outflow of blood from the dermal peripheral blood vessels. After two heartbeats, the pressure is lowered (secondary pressure) and blood reflows into the peripheral blood vessels. Hemoglobin concentration, which changes during blood outflow and reflow, is derived from the received light intensity using the Beer–Lambert law. This method was evaluated in 26 healthy female volunteers and 26 female scleroderma patients. In order to evaluate the blood circulation function of the peripheral blood vessels of scleroderma patients, pressurization sequence which consists of primary pressure followed by secondary pressure was adopted. Blood reflow during the first heartbeat period after applying the secondary pressure of 40mmHg was (mean±SD) 0.059±0.05%mm for scleroderma patients and 0.173±0.104%mm for healthy volunteers. Blood reflow was significantly lower in scleroderma patients than in healthy volunteers (p<0.05). This result indicates that the information necessary for assessing blood circulation disorder of peripheral blood vessels in scleroderma patients is objectively obtained by the proposed method. PMID:27479094

Evaluation of Peripheral Blood Circulation Disorder in Scleroderma Patients Using an Optical Sensor with a Pressurization Mechanism.

PubMed

Yamakoshi, Yoshiki; Motegi, Sei-Ichiro; Ishikawa, Osamu

2016-01-01

Blood circulation function of peripheral blood vessels in skin dermis was evaluated employing an optical sensor with a pressurization mechanism using the blood outflow and reflow characteristics. The device contains a light source and an optical sensor. When applied to the skin surface, it first exerts the primary pressure (higher than the systolic blood pressure), causing an outflow of blood from the dermal peripheral blood vessels. After two heartbeats, the pressure is lowered (secondary pressure) and blood reflows into the peripheral blood vessels. Hemoglobin concentration, which changes during blood outflow and reflow, is derived from the received light intensity using the Beer-Lambert law. This method was evaluated in 26 healthy female volunteers and 26 female scleroderma patients. In order to evaluate the blood circulation function of the peripheral blood vessels of scleroderma patients, pressurization sequence which consists of primary pressure followed by secondary pressure was adopted. Blood reflow during the first heartbeat period after applying the secondary pressure of 40mmHg was (mean±SD) 0.059±0.05%mm for scleroderma patients and 0.173±0.104%mm for healthy volunteers. Blood reflow was significantly lower in scleroderma patients than in healthy volunteers (p<0.05). This result indicates that the information necessary for assessing blood circulation disorder of peripheral blood vessels in scleroderma patients is objectively obtained by the proposed method.

Peripheral Refraction, Peripheral Eye Length, and Retinal Shape in Myopia.

PubMed

Verkicharla, Pavan K; Suheimat, Marwan; Schmid, Katrina L; Atchison, David A

2016-09-01

To investigate how peripheral refraction and peripheral eye length are related to retinal shape. Relative peripheral refraction (RPR) and relative peripheral eye length (RPEL) were determined in 36 young adults (M +0.75D to -5.25D) along horizontal and vertical visual field meridians out to ±35° and ±30°, respectively. Retinal shape was determined in terms of vertex radius of curvature Rv, asphericity Q, and equivalent radius of curvature REq using a partial coherence interferometry method involving peripheral eye lengths and model eye raytracing. Second-order polynomial fits were applied to RPR and RPEL as functions of visual field position. Linear regressions were determined for the fits' second order coefficients and for retinal shape estimates as functions of central spherical refraction. Linear regressions investigated relationships of RPR and RPEL with retinal shape estimates. Peripheral refraction, peripheral eye lengths, and retinal shapes were significantly affected by meridian and refraction. More positive (hyperopic) relative peripheral refraction, more negative RPELs, and steeper retinas were found along the horizontal than along the vertical meridian and in myopes than in emmetropes. RPR and RPEL, as represented by their second-order fit coefficients, correlated significantly with retinal shape represented by REq. Effects of meridian and refraction on RPR and RPEL patterns are consistent with effects on retinal shape. Patterns derived from one of these predict the others: more positive (hyperopic) RPR predicts more negative RPEL and steeper retinas, more negative RPEL predicts more positive relative peripheral refraction and steeper retinas, and steeper retinas derived from peripheral eye lengths predict more positive RPR.

[Peripheral refraction: cause or effect of refraction development?

PubMed

Tarutta, E P; Iomdina, E N; Kvaratskheliya, N G; Milash, S V; Kruzhkova, G V

to study peripheral refraction and the shape of the eyeball in children with different clinical refraction. Using an original method, peripheral refraction was measured at 10-12 degrees temporally and nasally from the fovea in 56 right eyes with different clinical, or axial, refraction of 20 boys and 36 girls aged 7 to 16 years (11.9±1.17 years on average). The shape of the eyeball was judged of by the ratio of its anterior-posterior axial length (AL) to horizontal diameter (HD). The incidence and value of peripheral myopic defocus in children appeared to decrease with clinical refraction increasing from high hyperopia to high myopia. This was the first time, mixed peripheral refraction was found in children, occurring more frequently in higher myopia. This mixed peripheral defocus, shown to be a transitional stage between relative peripheral myopia and relative hyperopia, indicates non-uniform stretching of posterior pole tissues in the course of refraction development and myopia progression. As ocular refraction increases from high hyperopia to high myopia, the growth of AL outpaces that of HD. Obviously, natural peripheral defocus results from changes in size and shape of the eyeball in the course of refraction development.

Single dose of filgrastim (rhG-CSF) increases the number of hematopoietic progenitors in the peripheral blood of adult volunteers.

PubMed

Schwinger, W; Mache, C; Urban, C; Beaufort, F; Töglhofer, W

1993-06-01

Hematopoietic progenitor cell levels were monitored in the peripheral blood of ten healthy adults receiving a single dose of recombinant human granulocyte colony-stimulating factor (rhG-CSF). The objective was to determine the time and number of progenitor cells released into the peripheral blood, induced by a single dose of 15 micrograms/kg rhG-CSF administered intravenously. In all cases the absolute number of circulating progenitor cells including granulocyte-macrophage and erythroid lineages increased up to 12-fold (median 9.4-fold) 4 days after treatment. These findings were based on flow cytometric quantification of CD34+ cells and on progenitor assays. The relative distribution of granulocyte/macrophage and erythroid progenitors remained unchanged. rhG-CSF was well tolerated; mild to moderate bone pain was the most common side-effect and was noted in 6 of 10 subjects. Thus a single dose of rhG-CSF is effective in mobilizing progenitor cells into the peripheral blood in healthy adults. If these progenitors are capable of reconstituting bone marrow, peripheral progenitor cell separation following rhG-CSF administration could be a reasonable alternative to conventional bone marrow harvest in healthy adults.

Peripheral Protein Unfolding Drives Membrane Bending.

PubMed

Siaw, Hew Ming Helen; Raghunath, Gokul; Dyer, R Brian

2018-06-20

Dynamic modulation of lipid membrane curvature can be achieved by a number of peripheral protein binding mechanisms such as hy-drophobic insertion of amphipathic helices and membrane scaffolding. Recently, an alternative mechanism was proposed in which crowding of peripherally bound proteins induces membrane curvature through steric pressure generated by lateral collisions. This effect was enhanced using intrinsically disordered proteins that possess high hydrodynamic radii, prompting us to explore whether membrane bending can be triggered by the folding-unfolding transition of surface-bound proteins. We utilized histidine-tagged human serum albumin bound to Ni-NTA-DGS containing liposomes as our model system to test this hypothesis. We found that reduction of the disulfide bonds in the protein resulted in unfolding of HSA, which subsequently led to membrane tubule formation. The frequency of tubule formation was found to be significantly higher when the proteins were unfolded while being localized to a phase-separated domain as opposed to randomly distributed in fluid phase liposomes, indicating that the steric pressure generated from protein unfolding is directly responsible for membrane deformation. Our results are critical for the design of peripheral membrane protein-immobilization strategies and open new avenues for exploring mechanisms of membrane bending driven by conformational changes of peripheral membrane proteins.

An integrated nanotechnology-enabled transbronchial image-guided intervention strategy for peripheral lung cancer

PubMed Central

Jin, Cheng S.; Wada, Hironobu; Anayama, Takashi; McVeigh, Patrick Z; Hu, Hsin Pei; Hirohashi, Kentaro; Nakajima, Takahiro; Kato, Tatsuya; Keshavjee, Shaf; Hwang, David; Wilson, Brian C.; Zheng, Gang; Yasufuku, Kazuhiro

2016-01-01

Early detection and efficient treatment modality of early-stage peripheral lung cancer is essential. Current non-surgical treatments for peripheral lung cancer show critical limitations associated with various complications, requiring alternative minimally invasive therapeutics. Porphysome nanoparticle-enabled fluorescence-guided transbronchial photothermal therapy (PTT) of peripheral lung cancer was developed and demonstrated in preclinical animal models. Systemically-administered porphysomes accumulated in lung tumors with significantly enhanced disease-to-normal tissue contrast, as confirmed in three subtypes of orthotopic human lung cancer xenografts (A549, H460 and H520) in mice and in an orthotopic VX2 tumor in rabbits. An in-house prototype fluorescence bronchoscope demonstrated the capability of porphysomes for in vivo imaging of lung tumors in the mucosal/submucosal layers, providing real-time fluorescence guidance for transbronchial PTT. Porphysomes also enhanced the efficacy of transbronchial PTT significantly and resulted in selective and efficient tumor tissue ablation in the rabbit model. A clinically used cylindrical diffuser fiber successfully achieved tumor-specific thermal ablation, showing promising evidence for the clinical translation of this novel platform to impact upon non-surgical treatment of early-stage peripheral lung cancer. PMID:27543602

Near-infrared signals associated with electrical stimulation of peripheral nerves

NASA Astrophysics Data System (ADS)

Fantini, Sergio; Chen, Debbie K.; Martin, Jeffrey M.; Sassaroli, Angelo; Bergethon, Peter R.

2009-02-01

We report our studies on the optical signals measured non-invasively on electrically stimulated peripheral nerves. The stimulation consists of the delivery of 0.1 ms current pulses, below the threshold for triggering any visible motion, to a peripheral nerve in human subjects (we have studied the sural nerve and the median nerve). In response to electrical stimulation, we observe an optical signal that peaks at about 100 ms post-stimulus, on a much longer time scale than the few milliseconds duration of the electrical response, or sensory nerve action potential (SNAP). While the 100 ms optical signal we measured is not a direct optical signature of neural activation, it is nevertheless indicative of a mediated response to neural activation. We argue that this may provide information useful for understanding the origin of the fast optical signal (also on a 100 ms time scale) that has been measured non-invasively in the brain in response to cerebral activation. Furthermore, the optical response to peripheral nerve activation may be developed into a diagnostic tool for peripheral neuropathies, as suggested by the delayed optical signals (average peak time: 230 ms) measured in patients with diabetic neuropathy with respect to normal subjects (average peak time: 160 ms).

Novel Automated Blood Separations Validate Whole Cell Biomarkers

PubMed Central

Burger, Douglas E.; Wang, Limei; Ban, Liqin; Okubo, Yoshiaki; Kühtreiber, Willem M.; Leichliter, Ashley K.; Faustman, Denise L.

2011-01-01

Background Progress in clinical trials in infectious disease, autoimmunity, and cancer is stymied by a dearth of successful whole cell biomarkers for peripheral blood lymphocytes (PBLs). Successful biomarkers could help to track drug effects at early time points in clinical trials to prevent costly trial failures late in development. One major obstacle is the inaccuracy of Ficoll density centrifugation, the decades-old method of separating PBLs from the abundant red blood cells (RBCs) of fresh blood samples. Methods and Findings To replace the Ficoll method, we developed and studied a novel blood-based magnetic separation method. The magnetic method strikingly surpassed Ficoll in viability, purity and yield of PBLs. To reduce labor, we developed an automated platform and compared two magnet configurations for cell separations. These more accurate and labor-saving magnet configurations allowed the lymphocytes to be tested in bioassays for rare antigen-specific T cells. The automated method succeeded at identifying 79% of patients with the rare PBLs of interest as compared with Ficoll's uniform failure. We validated improved upfront blood processing and show accurate detection of rare antigen-specific lymphocytes. Conclusions Improving, automating and standardizing lymphocyte detections from whole blood may facilitate development of new cell-based biomarkers for human diseases. Improved upfront blood processes may lead to broad improvements in monitoring early trial outcome measurements in human clinical trials. PMID:21799852

Sleep Deprivation Impairs the Human Central and Peripheral Nervous System Discrimination of Social Threat

PubMed Central

Goldstein-Piekarski, Andrea N.; Greer, Stephanie M.; Saletin, Jared M.

2015-01-01

Facial expressions represent one of the most salient cues in our environment. They communicate the affective state and intent of an individual and, if interpreted correctly, adaptively influence the behavior of others in return. Processing of such affective stimuli is known to require reciprocal signaling between central viscerosensory brain regions and peripheral-autonomic body systems, culminating in accurate emotion discrimination. Despite emerging links between sleep and affective regulation, the impact of sleep loss on the discrimination of complex social emotions within and between the CNS and PNS remains unknown. Here, we demonstrate in humans that sleep deprivation impairs both viscerosensory brain (anterior insula, anterior cingulate cortex, amygdala) and autonomic-cardiac discrimination of threatening from affiliative facial cues. Moreover, sleep deprivation significantly degrades the normally reciprocal associations between these central and peripheral emotion-signaling systems, most prominent at the level of cardiac-amygdala coupling. In addition, REM sleep physiology across the sleep-rested night significantly predicts the next-day success of emotional discrimination within this viscerosensory network across individuals, suggesting a role for REM sleep in affective brain recalibration. Together, these findings establish that sleep deprivation compromises the faithful signaling of, and the “embodied” reciprocity between, viscerosensory brain and peripheral autonomic body processing of complex social signals. Such impairments hold ecological relevance in professional contexts in which the need for accurate interpretation of social cues is paramount yet insufficient sleep is pervasive. PMID:26180190

Novel Familial Variant of the Desert Hedgehog Gene: Clinical Findings in Two Sisters with 46,XY Gonadal Dysgenesis or 46,XX Karyotype and Literature Review.

PubMed

Baldinotti, Fulvia; Cavallaro, Tiziana; Dati, Eleonora; Baroncelli, Giampiero I; Bertini, Veronica; Valetto, Angelo; Massart, Francesco; Fabrizi, Gian Maria; Zanette, Giampietro; Peroni, Diego; Bertelloni, Silvano

2018-01-01

In humans, Desert Hedgehog (DHH) gene mutations are a very rare cause of 46,XY gonadal dysgenesis (GD), eventually associated with peripheral neuropathy. Clinical records of 12 patients with 46,XY GD and unknown genetic background were reviewed and a 46,XY woman with peripheral neuropathy was individuated. Her 46,XX sister affected by similar neuropathy was also investigated. Genomic DNA was extracted and DHH exons sequenced and analyzed. A comparative genomic hybridization array was also performed. In both the 46,XY and 46,XX sisters, a homozygous c.554C>A mutation in exon 2 of the DHH gene was found, determining a premature termination codon (p.Ser 185*). Heterozygous consanguineous carrier parents showed neither reproductive problems nor peripheral neuropathy. In the proband and her sister, a 499-kb duplication in 9p22.1 was also found. A 46,XY European woman with 46,XY GD and a novel homozygous DHH pathogenic variant is reported, confirming that this gene plays a key role in male gonadal development. Her 46,XX sister, harboring the same mutation, showed normal internal and external female phenotype. Thus, DHH seems not to be involved in the ovarian development pathway or its postpubertal function. Homozygous DHH mutations cause a specific peripheral neuropathy in humans with both 46,XY and 46,XX karyotypes. © 2018 S. Karger AG, Basel.

Sleep Deprivation Impairs the Human Central and Peripheral Nervous System Discrimination of Social Threat.

PubMed

Goldstein-Piekarski, Andrea N; Greer, Stephanie M; Saletin, Jared M; Walker, Matthew P

2015-07-15

Facial expressions represent one of the most salient cues in our environment. They communicate the affective state and intent of an individual and, if interpreted correctly, adaptively influence the behavior of others in return. Processing of such affective stimuli is known to require reciprocal signaling between central viscerosensory brain regions and peripheral-autonomic body systems, culminating in accurate emotion discrimination. Despite emerging links between sleep and affective regulation, the impact of sleep loss on the discrimination of complex social emotions within and between the CNS and PNS remains unknown. Here, we demonstrate in humans that sleep deprivation impairs both viscerosensory brain (anterior insula, anterior cingulate cortex, amygdala) and autonomic-cardiac discrimination of threatening from affiliative facial cues. Moreover, sleep deprivation significantly degrades the normally reciprocal associations between these central and peripheral emotion-signaling systems, most prominent at the level of cardiac-amygdala coupling. In addition, REM sleep physiology across the sleep-rested night significantly predicts the next-day success of emotional discrimination within this viscerosensory network across individuals, suggesting a role for REM sleep in affective brain recalibration. Together, these findings establish that sleep deprivation compromises the faithful signaling of, and the "embodied" reciprocity between, viscerosensory brain and peripheral autonomic body processing of complex social signals. Such impairments hold ecological relevance in professional contexts in which the need for accurate interpretation of social cues is paramount yet insufficient sleep is pervasive. Copyright © 2015 the authors 0270-6474/15/3510135-11$15.00/0.

21 CFR 882.5870 - Implanted peripheral nerve stimulator for pain relief.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882... the stimulating pulses across the patient's skin to the implanted receiver. (b) Classification. Class...

Quantification of cytokine mRNA in peripheral blood mononuclear cells using branched DNA (bDNA) technology.

PubMed

Shen, L P; Sheridan, P; Cao, W W; Dailey, P J; Salazar-Gonzalez, J F; Breen, E C; Fahey, J L; Urdea, M S; Kolberg, J A

1998-06-01

Changes in the patterns of cytokine expression are thought to be of central importance in human infectious and inflammatory diseases. As such, there is a need for precise, reproducible assays for quantification of cytokine mRNA that are amenable to routine use in a clinical setting. In this report, we describe the design and performance of a branched DNA (bDNA) assay for the direct quantification of multiple cytokine mRNA levels in peripheral blood mononuclear cells (PBMCs). Oligonucleotide target probe sets were designed for several human cytokines, including TNFalpha, IL-2, IL-4, IL-6, IL-10, and IFNgamma. The bDNA assay yielded highly reproducible quantification of cytokine mRNAs, exhibited a broad linear dynamic range of over 3-log10, and showed a sensitivity sufficient to measure at least 3000 molecules. The potential clinical utility of the bDNA assay was explored by measuring cytokine mRNA levels in PBMCs from healthy and immunocompromised individuals. Cytokine expression levels in PBMCs from healthy blood donors were found to remain relatively stable over a one-month period of time. Elevated levels of IFNgamma mRNA were detected in PBMCs from HIV-1 seropositive individuals, but no differences in mean levels of TNFalpha or IL-6 mRNA were detected between seropositive and seronegative individuals. By providing a reproducible method for quantification of low abundance transcripts in clinical specimens, the bDNA assay may be useful for studies addressing the role of cytokine expression in disease.

[Mobilization of autologous peripheral blood stem cells by cyclophosphamide and recombinant human granulocyte colony-stimulating factor(rhG-CSF)].

PubMed

Shi, Y; Zhou, S; Han, X

1998-08-01

To observe the effect of cyclophosphamide (CTX) and recombinant human granulocyte colony-stimulating factor(rhG-CSF, Filgrastim) on autologous peripheral blood stem cells (APBSC) mobilization. CTX (3.7 +/- 0.2) g/m2 was intravenously injected the first day. rhG-CSF (4.5 +/- 0.6) micrograms.kg-1.d-1 was injected subcutaneously from the day of white blood cell (WBC) nadir to the day before the end of APBSC harvest. APBSC harvest was started when WBC > 2.5 x 10(9)/L and finished when accumulated mononuclear cells (MNC) of APBSC > 5 x 10(8)/kg. CFU-GM, BFU-E culture and CD34+ cells detection of the APBSC was performed. Twenty cases underwent the APBSC mobilization. The nadir of WBC was (1.1 +/- 0.5) x 10(9)/L at day (9 +/- 1). rhG-CSF was injected from day (10 +/- 1) and continued for (6 +/- 1) days. APBSC harvest began on day (13 +/- 1) and continued for (4 +/- 1) days. Accumulated MNC harvest was (8.4 +/- 1.9) x 10(8)/kg, CFU-GM (18.7 +/- 10.3) x 10(4)/kg, BFU-E (18.5 +/- 8.7) x 10(4)/kg, and CD34+ cells (20.9 +/- 5.7) x 10(6)/kg. No severe toxicity was observed. Hematopoietic reconstitution was very well in 18 patients received the APBSC transplantation. CTX combined with rhG-CSF was a safe and highly effective method for APBSC mobilization.

Intradermal administration of magnesium sulphate and magnesium chloride produces hypesthesia to mechanical but hyperalgesia to heat stimuli in humans

PubMed Central

Ushida, Takahiro; Iwatsu, Osamu; Shimo, Kazuhiro; Tetsunaga, Tomoko; Ikeuchi, Masahiko; Ikemoto, Tatsunori; Arai, Young-Chang P; Suetomi, Katsutoshi; Nishihara, Makoto

2009-01-01

Background Although magnesium ions (Mg2+) are known to display many similar features to other 2+ charged cations, they seem to have quite an important and unique role in biological settings, such as NMDA blocking effect. However, the role of Mg2+ in the neural transmission system has not been studied as sufficiently as calcium ions (Ca2+). To clarify the sensory effects of Mg2+ in peripheral nervous systems, sensory changes after intradermal injection of Mg2+ were studied in humans. Methods Magnesium sulphate, magnesium chloride and saline were injected into the skin of the anterior region of forearms in healthy volunteers and injection-induced irritating pain ("irritating pain", for short), tactile sensation, tactile pressure thresholds, pinch-pain changes and intolerable heat pain thresholds of the lesion were monitored. Results Flare formation was observed immediately after magnesium sulphate or magnesium chloride injection. We found that intradermal injections of magnesium sulphate and magnesium chloride transiently caused irritating pain, hypesthesia to noxious and innocuous mechanical stimulations, whereas secondary hyperalgesia due to mechanical stimuli was not observed. In contrast to mechanical stimuli, intolerable heat pain-evoking temperature was significantly decreased at the injection site. In addition to these results, spontaneous pain was immediately attenuated by local cooling. Conclusion Membrane-stabilizing effect and peripheral NMDA-blocking effect possibly produced magnesium-induced mechanical hypesthesia, and extracellular cation-induced sensitization of TRPV1 channels was thought to be the primary mechanism of magnesium-induced heat hyperalgesia. PMID:19715604

Accumulation of human T lymphotropic virus (HTLV)-I-specific T cell clones in HTLV-I-associated myelopathy/tropical spastic paraparesis patients.

PubMed

Höger, T A; Jacobson, S; Kawanishi, T; Kato, T; Nishioka, K; Yamamoto, K

1997-08-15

Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraperesis (HAM/TSP) is a slowly progressive neurologic disorder following infection with HTLV-I. It is characterized by spasticity and hyper-reflexia of the lower extremities, urinary bladder disturbance, lower extremity muscle weakness, and sensory disturbances. HTLV-I, as an inducer of a strong humoral and cytotoxic response, is a well-known pathogenic factor for the progression of HAM/TSP. Peptides derived from proviral tax and env genes provide epitopes recognized by T cells. We herein report an accumulation of distinct clonotypes of alpha/beta TCR+ peripheral blood T lymphocytes from HAM/TSP patients in comparison with that observed in both asymptomatic carriers and healthy controls, using the reverse-transcriptase PCR/single-strand conformation polymorphism method. We also found that some of the accumulated T cell clones in the peripheral blood and cerebrospinal fluid are HTLV-I Tax(11-19) peptide specific. Such clones were found to expand strongly after being cultured with an HTLV-I Tax(11-19) peptide. Moreover, the cultured samples exhibited a strong MHC class I-restricted cytotoxic activity against HTLV-I Tax(11-19) peptide-expressing targets, and therefore most likely also include the disease-associated T cell clones observed in the patients. This is the first report of a direct assessment of Ag-specific T cell responses in fresh PBL and cerebrospinal fluid.

DNA methylome profiling of maternal peripheral blood and placentas reveal potential fetal DNA markers for non-invasive prenatal testing.

PubMed

Xiang, Yuqian; Zhang, Junyu; Li, Qiaoli; Zhou, Xinyao; Wang, Teng; Xu, Mingqing; Xia, Shihui; Xing, Qinghe; Wang, Lei; He, Lin; Zhao, Xinzhi

2014-09-01

Utilizing epigenetic (DNA methylation) differences to differentiate between maternal peripheral blood (PBL) and fetal (placental) DNA has been a promising strategy for non-invasive prenatal testing (NIPT). However, the differentially methylated regions (DMRs) have yet to be fully ascertained. In the present study, we performed genome-wide comparative methylome analysis between maternal PBL and placental DNA from pregnancies of first trimester by methylated DNA immunoprecipitation-sequencing (MeDIP-Seq) and Infinium HumanMethylation450 BeadChip assays. A total of 36 931 DMRs and 45 804 differentially methylated sites (DMSs) covering the whole genome, exclusive of the Y chromosome, were identified via MeDIP-Seq and Infinium 450k array, respectively, of which 3759 sites in 2188 regions were confirmed by both methods. Not only did we find the previously reported potential fetal DNA markers in our identified DMRs/DMSs but also we verified fully the identified DMRs/DMSs in the validation round by MassARRAY EpiTYPER. The screened potential fetal DNA markers may be used for NIPT on aneuploidies and other chromosomal diseases, such as cri du chat syndrome and velo-cardio-facial syndrome. In addition, these potential markers may have application in the early diagnosis of placental dysfunction, such as pre-eclampsia. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

HIV-1 infection, response to treatment and establishment of viral latency in a novel humanized T cell-only mouse (TOM) model.

PubMed

Honeycutt, Jenna B; Wahl, Angela; Archin, Nancie; Choudhary, Shailesh; Margolis, David; Garcia, J Victor

2013-10-24

The major targets of HIV infection in humans are CD4⁺ T cells. CD4⁺ T cell depletion is a hallmark of AIDS. Previously, the SCID-hu thy/liv model was used to study the effect of HIV on thymopoeisis in vivo. However, these mice did not develop high levels of peripheral T cell reconstitution and required invasive surgery for infection and analysis. Here, we describe a novel variant of this model in which thy/liv implantation results in systemic reconstitution with human T cells in the absence of any other human hematopoietic lineages. NOD/SCID-hu thy/liv and NSG-hu thy/liv mice were created by implanting human fetal thymus and liver tissues under the kidney capsule of either NOD/SCID or NSG mice. In contrast to NOD/SCID-hu thy/liv mice that show little or no human cells in peripheral blood or tissues, substantial systemic human reconstitution occurs in NSG-hu thy/liv. These mice are exclusively reconstituted with human T cells (i.e. T-cell only mice or TOM). Despite substantial levels of human T cells no signs of graft-versus-host disease (GVHD) were noted in these mice over a period of 14 months. TOM are readily infected after parenteral exposure to HIV-1. HIV replication is sustained in peripheral blood at high levels and results in modest reduction of CD4⁺ T cells. HIV-1 replication in TOM responds to daily administration of combination antiretroviral therapy (ART) resulting in strong suppression of virus replication as determined by undetectable viral load in plasma. Latently HIV infected resting CD4⁺ T cells can be isolated from suppressed mice that can be induced to express HIV ex-vivo upon activation demonstrating the establishment of latency in vivo. NSG-hu thy/liv mice are systemically reconstituted with human T cells. No other human lymphoid lineages are present in these mice (i.e. monocytes/macrophages, B cells and DC are all absent). These T cell only mice do not develop GVHD, are susceptible to HIV-1 infection and can efficiently maintain virus replication. HIV infected TOM undergoing ART harbor latently infected, resting CD4+ T cells.

The Fc and not CD4 Receptor Mediates Antibody Enhancement of HIV Infection in Human Cells

NASA Astrophysics Data System (ADS)

Homsy, Jacques; Meyer, Mia; Tateno, Masatoshi; Clarkson, Sarah; Levy, Jay A.

1989-06-01

Antibodies that enhance human immunodeficiency virus (HIV) infectivity have been found in the blood of infected individuals and in infected or immunized animals. These findings raise serious concern for the development of a safe vaccine against acquired immunodeficiency syndrome. To address the in vivo relevance and mechanism of this phenomenon, antibody-dependent enhancement of HIV infectivity in peripheral blood macrophages, lymphocytes, and human fibroblastoid cells was studied. Neither Leu3a, a monoclonal antibody directed against the CD4 receptor, nor soluble recombinant CD4 even at high concentrations prevented this enhancement. The addition of monoclonal antibody to the Fc receptor III (anti-FcRIII), but not of antibodies that react with FcRI or FcRII, inhibited HIV type 1 and HIV type 2 enhancement in peripheral blood macrophages. Although enhancement of HIV infection in CD4+ lymphocytes could not be blocked by anti-FcRIII, it was inhibited by the addition of human immunoglobulin G aggregates. The results indicate that the FcRIII receptor on human macrophages and possibly another Fc receptor on human CD4+ lymphocytes mediate antibody-dependent enhancement of HIV infectivity and that this phenomenon proceeds through a mechanism independent of the CD4 protein.

Systematic review of vestibular disorders related to human immunodeficiency virus and acquired immunodeficiency syndrome.

PubMed

Heinze, B; Swanepoel, D W; Hofmeyr, L M

2011-09-01

Disorders of the auditory and vestibular system are often associated with human immunodeficiency virus infection and acquired immunodeficiency syndrome. However, the extent and nature of these vestibular manifestations are unclear. To systematically review the current peer-reviewed literature on vestibular manifestations and pathology related to human immunodeficiency virus and acquired immunodeficiency syndrome. Systematic review of peer-reviewed articles related to vestibular findings in individuals with human immunodeficiency virus infection and acquired immunodeficiency syndrome. Several electronic databases were searched. We identified 442 records, reduced to 210 after excluding duplicates and reviews. These were reviewed for relevance to the scope of the study. We identified only 13 reports investigating vestibular functioning and pathology in individuals affected by human immunodeficiency virus and acquired immunodeficiency syndrome. This condition can affect both the peripheral and central vestibular system, irrespective of age and viral disease stage. Peripheral vestibular involvement may affect up to 50 per cent of patients, and central vestibular involvement may be even more prevalent. Post-mortem studies suggest direct involvement of the entire vestibular system, while opportunistic infections such as oto- and neurosyphilis and encephalitis cause secondary vestibular dysfunction resulting in vertigo, dizziness and imbalance. Patients with human immunodeficiency virus and acquired immunodeficiency syndrome should routinely be monitored for vestibular involvement, to minimise functional limitations of quality of life.

Peripheral surgical wounding may induce cognitive impairment through interlukin-6-dependent mechanisms in aged mice.

PubMed

Dong, Yuanlin; Xu, Zhipeng; Huang, Lining; Zhang, Yiying; Xie, Zhongcong

2016-01-01

Post-operative cognitive dysfunction (POCD) is associated with morbidity, mortality and increased cost of medical care. However, the neuropathogenesis and targeted interventions of POCD remain largely to be determined. We have found that the peripheral surgical wounding induces an age-dependent Aβ accumulation, neuroinflammation and cognitive impairment in aged mice. Pro-inflammatory cytokine interlukin-6 (IL-6) has been reported to be associated with cognitive impairment in rodents and humans. However, the role of IL-6 in the neuropathogenesis of POCD is unknown. We therefore employed pharmacological (IL-6 antibody) and genetic (knockout of IL-6) approach to investigate whether IL-6 contributed to the peripheral surgical wounding-induced cognitive impairment in aged mice. Abdominal surgery under local anesthesia (peripheral surgical wounding) was established in 18-month-old wild-type and IL-6 knockout mice ( n = 6 to 10 in each group). Brain level of IL-6 and cognitive function in the mice were determined by western blot, ELISA at the end of procedure, and Fear Conditioning System at 7 days after the procedure. The peripheral surgical wounding increased the level of IL-6 in the hippocampus of aged wild-type, but not IL-6 knockout mice. IL-6 antibody ameliorated the peripheral surgical wounding-induced cognitive impairment in the aged wild-type mice. Finally, the peripheral surgical wounding did not induce cognitive impairment in the aged IL-6 knockout mice. These data suggested that IL-6 would be a required pro-inflammatory cytokine for the peripheral surgical wounding-induced cognitive impairment. Given this, further studies are warranted to investigate the role of IL-6 in the neuropathogenesis and targeted interventions of POCD.

Evidence from Human and Animal Studies: Pathological Roles of CD8+ T Cells in Autoimmune Peripheral Neuropathies

PubMed Central

Yang, Mu; Peyret, Corentin; Shi, Xiang Qun; Siron, Nicolas; Jang, Jeong Ho; Wu, Sonia; Fournier, Sylvie; Zhang, Ji

2015-01-01

Autoimmune peripheral neuropathies such as Guillain-Barre Syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) affect millions of people worldwide. Despite significant advances in understanding the pathology, the molecular and cellular mechanisms of immune-mediated neuropathies remain elusive. T lymphocytes definitely play an important role in disease pathogenesis and CD4+ T cells have been the main area of research for decades. This is partly due to the fact that the most frequent animal model to study autoimmune peripheral neuropathy is experimental allergic neuritis (EAN). As it is induced commonly by immunization with peripheral nerve proteins, EAN is driven mainly by CD4+ T cells. However, similarly to what has been reported for patients suffering from multiple sclerosis, a significant body of evidence indicates that CD8+ T cells may play a pathogenic role in GBS and CIDP disease development and/or progression. Here, we summarize clinical studies pertaining to the presence and potential role of CD8+ T cells in autoimmune peripheral neuropathies. We also discuss the findings from our most recent studies using a transgenic mouse line (L31 mice) in which the T cell co-stimulator molecule B7.2 (CD86) is constitutively expressed in antigen presenting cells of the nervous tissues. L31 mice spontaneously develop peripheral neuropathy, and CD8+ T cells are found accumulating in peripheral nerves of symptomatic animals. Interestingly, depletion of CD4+ T cells accelerates disease onset and increases disease prevalence. Finally, we point out some unanswered questions for future research to dissect the critical roles of CD8+ T cells in autoimmune peripheral neuropathies. PMID:26528293

Evidence from Human and Animal Studies: Pathological Roles of CD8(+) T Cells in Autoimmune Peripheral Neuropathies.

PubMed

Yang, Mu; Peyret, Corentin; Shi, Xiang Qun; Siron, Nicolas; Jang, Jeong Ho; Wu, Sonia; Fournier, Sylvie; Zhang, Ji

2015-01-01

Autoimmune peripheral neuropathies such as Guillain-Barre Syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) affect millions of people worldwide. Despite significant advances in understanding the pathology, the molecular and cellular mechanisms of immune-mediated neuropathies remain elusive. T lymphocytes definitely play an important role in disease pathogenesis and CD4(+) T cells have been the main area of research for decades. This is partly due to the fact that the most frequent animal model to study autoimmune peripheral neuropathy is experimental allergic neuritis (EAN). As it is induced commonly by immunization with peripheral nerve proteins, EAN is driven mainly by CD4(+) T cells. However, similarly to what has been reported for patients suffering from multiple sclerosis, a significant body of evidence indicates that CD8(+) T cells may play a pathogenic role in GBS and CIDP disease development and/or progression. Here, we summarize clinical studies pertaining to the presence and potential role of CD8(+) T cells in autoimmune peripheral neuropathies. We also discuss the findings from our most recent studies using a transgenic mouse line (L31 mice) in which the T cell co-stimulator molecule B7.2 (CD86) is constitutively expressed in antigen presenting cells of the nervous tissues. L31 mice spontaneously develop peripheral neuropathy, and CD8(+) T cells are found accumulating in peripheral nerves of symptomatic animals. Interestingly, depletion of CD4(+) T cells accelerates disease onset and increases disease prevalence. Finally, we point out some unanswered questions for future research to dissect the critical roles of CD8(+) T cells in autoimmune peripheral neuropathies.

Peripheral surgical wounding may induce cognitive impairment through interlukin-6-dependent mechanisms in aged mice

PubMed Central

Dong, Yuanlin; Xu, Zhipeng; Huang, Lining; Zhang, Yiying; Xie, Zhongcong

2016-01-01

Post-operative cognitive dysfunction (POCD) is associated with morbidity, mortality and increased cost of medical care. However, the neuropathogenesis and targeted interventions of POCD remain largely to be determined. We have found that the peripheral surgical wounding induces an age-dependent Aβ accumulation, neuroinflammation and cognitive impairment in aged mice. Pro-inflammatory cytokine interlukin-6 (IL-6) has been reported to be associated with cognitive impairment in rodents and humans. However, the role of IL-6 in the neuropathogenesis of POCD is unknown. We therefore employed pharmacological (IL-6 antibody) and genetic (knockout of IL-6) approach to investigate whether IL-6 contributed to the peripheral surgical wounding-induced cognitive impairment in aged mice. Abdominal surgery under local anesthesia (peripheral surgical wounding) was established in 18-month-old wild-type and IL-6 knockout mice (n = 6 to 10 in each group). Brain level of IL-6 and cognitive function in the mice were determined by western blot, ELISA at the end of procedure, and Fear Conditioning System at 7 days after the procedure. The peripheral surgical wounding increased the level of IL-6 in the hippocampus of aged wild-type, but not IL-6 knockout mice. IL-6 antibody ameliorated the peripheral surgical wounding-induced cognitive impairment in the aged wild-type mice. Finally, the peripheral surgical wounding did not induce cognitive impairment in the aged IL-6 knockout mice. These data suggested that IL-6 would be a required pro-inflammatory cytokine for the peripheral surgical wounding-induced cognitive impairment. Given this, further studies are warranted to investigate the role of IL-6 in the neuropathogenesis and targeted interventions of POCD. PMID:28217289

Environmental risk assessment of wastewaters from printed circuit board production: A multibiomarker approach using human cells.

PubMed

Gerić, Marko; Gajski, Goran; Oreščanin, Višnja; Domijan, Ana-Marija; Kollar, Robert; Garaj-Vrhovac, Vera

2017-02-01

Since the production of printed circuit boards (PCBs) generates wastewater contaminated with heavy metals and organic matter, PCB factories represent potential pollution sites. The wastewater toxicologically tested in this study contained several metals and the most abundant were copper and iron. At two exposure times tested (4 and 24 h) PCB wastewater (PCBW) proved to be cytotoxic (decreased cell viability) and genotoxic (increased comet assay tail intensity and tail moment) to human blood peripheral lymphocytes in vitro, and the oxidative stress parameter (malondialdehyde concentration) was also found to be higher. After application of combined treatment by waste base, ozone and waste sludge methods, concentrations of metals in purified PCBW were below the upper permitted levels and all tested toxicological parameters did not differ compared to the negative control. Taken together, similar methods could be implemented in PCB factories before discharging potentially toxic wastewater into the environment because purified PCBW does not represent a threat from the aspect of cytotoxicity and genotoxicity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Efficient production by sperm-mediated gene transfer of human decay accelerating factor (hDAF) transgenic pigs for xenotransplantation

PubMed Central

Lavitrano, Marialuisa; Bacci, Maria Laura; Forni, Monica; Lazzereschi, Davide; Di Stefano, Carla; Fioretti, Daniela; Giancotti, Paola; Marfé, Gabriella; Pucci, Loredana; Renzi, Luigina; Wang, Hongjun; Stoppacciaro, Antonella; Stassi, Giorgio; Sargiacomo, Massimo; Sinibaldi, Paola; Turchi, Valeria; Giovannoni, Roberto; Della Casa, Giacinto; Seren, Eraldo; Rossi, Giancarlo

2002-01-01

A large number of hDAF transgenic pigs to be used for xenotransplantation research were generated by using sperm-mediated gene transfer (SMGT). The efficiency of transgenesis obtained with SMGT was much greater than with any other method. In the experiments reported, up to 80% of pigs had the transgene integrated into the genome. Most of the pigs carrying the hDAF gene transcribed it in a stable manner (64%). The great majority of pigs that transcribed the gene expressed the protein (83%). The hDAF gene was transmitted to progeny. Expression was stable and found in caveolae as it is in human cells. The expressed gene was functional based on in vitro experiments performed on peripheral blood mononuclear cells. These results show that our SMGT approach to transgenesis provides an efficient procedure for studies involving large animal models. PMID:12393815

In vitro antigen-specific induction of IL-22 in human subjects that resolved HCV infection

PubMed Central

Cusick, Matthew F; Libbey, Jane E; Fujinami, Robert S; Eckels, David D

2012-01-01

Aims To determine if in vitro production of IL-22 and IL-17 correlated with resolution of HCV infection. Materials & methods Human peripheral blood cells isolated from a well-defined cohort of resolved and chronic HCV-infected subjects were used to measure HCV-, influenza- and mitogen-activated T-cell proliferation. In addition, IL-22 and IL-17 production was measured via ELISAs and flow cytometry. Results Resolved HCV subjects had a significantly higher T-cell proliferative response to recombinant NS3 protein compared with chronic HCV subjects. Resolved subjects had a dose-dependent IL-22 response to recombinant NS3 compared with chronic HCV subjects. Conclusion IL-22 production is associated with antigen-specific induction of CD4 + T cells in individuals that resolved HCV infection, suggesting a potential role for IL-22 in HCV clearance. PMID:23185211

Isolation of Human Innate Lymphoid Cells.

PubMed

Krabbendam, Lisette; Nagasawa, Maho; Spits, Hergen; Bal, Suzanne M

2018-06-29

Innate lymphoid cells (ILCs) are innate immune cells of lymphoid origin that have important effector and regulatory functions in the first line of defense against pathogens, but also regulate tissue homeostasis, remodeling, and repair. Their function mirrors T helper cells and cytotoxic CD8 + T lymphocytes, but they lack expression of rearranged antigen-specific receptors. Distinct ILC subsets are classified in group 1 ILCs (ILC1s), group 2 ILCs (ILC2s), and group 3 ILCs (ILC3s and lymphoid tissue-inducer cells), based on the expression of transcription factors and the cytokines they produce. As the frequency of ILCs is low, their isolation requires extensive depletion of other cell types. The lack of unique cell surface antigens further complicates the identification of these cells. Here, methods for ILC isolation and characterization from human peripheral blood and different tissues are described. © 2018 by John Wiley & Sons, Inc. © 2018 John Wiley & Sons, Inc.

On the Modeling of Electrical Effects Experienced by Space Explorers During Extra Vehicular Activities: Intracorporal Currents, Resistances, and Electric Fields

NASA Technical Reports Server (NTRS)

Cela, Carlos J.; Loizos, Kyle; Lazzi, Gianluca; Hamilton, Douglas; Lee, Raphael C.

2011-01-01

Recent research has shown that space explorers engaged in Extra Vehicular Activities (EVAs) may be exposed, under certain conditions, to undesired electrical currents. This work focuses on determining whether these undesired induced electrical currents could be responsible for involuntary neuromuscular activity in the subjects, possibly caused by either large diameter peripheral nerve activation or reflex activity from cutaneous afferent stimulation. An efficient multiresolution variant of the admittance method along with a millimeter-resolution model of a male human body were used to calculate induced electric fields, resistance between contact electrodes used to simulate the potential exposure condition, and currents induced in the human body model. Results show that, under realistic exposure conditions using a 15V source, current density magnitudes and total current injected are well above previously reported startle reaction thresholds. This indicates that, under the considered conditions, the subjects could experience involuntary motor response.

Induction and identification of rabbit peripheral blood derived dendritic cells

NASA Astrophysics Data System (ADS)

Zhou, Jing; Yang, FuYuan; Chen, WenLi

2012-03-01

Purpose: To study a method of the induction of dendritic cells (DCs) from rabbit peripheral blood. Methods: Peripheral blood cells were removed from rabbit, filtered through nylon mesh. Peripheral blood mononuclear cells (PBMC) were isolated from the blood cells by Ficoll-Hypaque centrifugation (density of 1.077g/cm3).To obtain DCs, PBMC were cultured in RPMI1640 medium containing 10% fetal calf serum, 50U/mL penicillin and streptomycin, referred to subsequently as complete medium, at 37°C in 5% CO2 atmosphere for 4 hours. Nonadherent cells were aspirated, adherent cells were continued incubated in complete medium, supplemented with granulocyte/macrophage colony-stimulating factor (GM-CSF, 50ng/ml),and interleukin 4 (IL-4, 50ng/ml) for 9 days. Fluorescein labeled antibodies(anti-CD14, anti-HLA-DR, anti-CD86) were used to sign cells cultured for 3,6,9 days respectively, Then flow cytometry was performed. Results: Ratio of anti-HLA-DR and anti-CD86 labeled cells increased with induction time extension, in contrast with anti-CD14. Conclusion: Dendritic cells can be effectively induced by the method of this experiment, cell maturation status increased with induction time extension.

Cerebellum tunes the excitability of the motor system: evidence from peripheral motor axons.

PubMed

Nodera, Hiroyuki; Manto, Mario

2014-12-01

Cerebellum is highly connected with the contralateral cerebral cortex. So far, the motor deficits observed in acute focal cerebellar lesions in human have been mainly explained on the basis of a disruption of the cerebello-thalamo-cortical projections. Cerebellar circuits have also numerous anatomical and functional interactions with brainstem nuclei and projects also directly to the spinal cord. Cerebellar lesions alter the excitability of peripheral motor axons as demonstrated by peripheral motor threshold-tracking techniques in cerebellar stroke. The biophysical changes are correlated with the functional scores. Nerve excitability measurements represent an attractive tool to extract the rules underlying the tuning of excitability of the motor pathways by the cerebellum and to discover the contributions of each cerebellar nucleus in this key function, contributing to early plasticity and sensorimotor learning.

A modification of the fusion model for log polar coordinates

NASA Technical Reports Server (NTRS)

Griswold, N. C.; Weiman, Carl F. R.

1990-01-01

The fusion mechanism for application in stereo analysis of range restricted the depth of field and therefore required a shift variant mechanism in the peripheral area to find disparity. Misregistration was prevented by restricting the disparity detection range to a neighborhood spanned by the directional edge detection filters. This transformation was essentially accomplished by a nonuniform resampling of the original image in a horizontal direction. While this is easily implemented for digital processing, the approach does not (in the peripheral vision area) model the log-conformal mapping which is known to occur in the human mechanism. This paper therefore modifies the original fusion concept in the peripheral area to include the polar exponential grid-to-log conformal tesselation. Examples of the fusion process resulting in accurate disparity values are given.

A microfluidic culture model of the human reproductive tract and 28-day menstrual cycle

PubMed Central

Xiao, Shuo; Coppeta, Jonathan R.; Rogers, Hunter B.; Isenberg, Brett C.; Zhu, Jie; Olalekan, Susan A.; McKinnon, Kelly E.; Dokic, Danijela; Rashedi, Alexandra S.; Haisenleder, Daniel J.; Malpani, Saurabh S.; Arnold-Murray, Chanel A.; Chen, Kuanwei; Jiang, Mingyang; Bai, Lu; Nguyen, Catherine T.; Zhang, Jiyang; Laronda, Monica M.; Hope, Thomas J.; Maniar, Kruti P.; Pavone, Mary Ellen; Avram, Michael J.; Sefton, Elizabeth C.; Getsios, Spiro; Burdette, Joanna E.; Kim, J. Julie; Borenstein, Jeffrey T.; Woodruff, Teresa K.

2017-01-01

The endocrine system dynamically controls tissue differentiation and homeostasis, but has not been studied using dynamic tissue culture paradigms. Here we show that a microfluidic system supports murine ovarian follicles to produce the human 28-day menstrual cycle hormone profile, which controls human female reproductive tract and peripheral tissue dynamics in single, dual and multiple unit microfluidic platforms (Solo-MFP, Duet-MFP and Quintet-MPF, respectively). These systems simulate the in vivo female reproductive tract and the endocrine loops between organ modules for the ovary, fallopian tube, uterus, cervix and liver, with a sustained circulating flow between all tissues. The reproductive tract tissues and peripheral organs integrated into a microfluidic platform, termed EVATAR, represents a powerful new in vitro tool that allows organ–organ integration of hormonal signalling as a phenocopy of menstrual cycle and pregnancy-like endocrine loops and has great potential to be used in drug discovery and toxicology studies. PMID:28350383

Mu-opiate receptor and Beta-endorphin expression in nerve endings and keratinocytes in human skin.

PubMed

Bigliardi-Qi, M; Sumanovski, L T; Büchner, S; Rufli, T; Bigliardi, P L

2004-01-01

We have previously shown that human epidermal keratinocytes express a functionally active micro-opiate receptor, which adds a new dimension to the recently developed research in neuroimmunodermatology and neurogenic inflammation in skin diseases. Human keratinocytes specifically bind and also produce beta-endorphin, the endogenous micro-opiate receptor ligand. Using confocal imaging microscopy, we could now demonstrate that micro-opiate receptors are not only expressed in keratinocytes, but also on unmyelinated peripheral nerve fibers in the dermis and epidermis. Some of the peripheral nerve fibers also express the ligand beta-endorphin. The keratinocytes positive for beta-endorphin staining are clustered around the terminal ends of the unmyelinated nerve fibers. Therefore the opiate receptor system seems to be crucial in the direct communication between nerves and skin. The keratinocytes can influence the unmyelinated nerve fibers in the epidermis directly via secreting beta-endorphin. On the other hand, nerve fibers can also secrete beta-endorphin and influence the migration, differentiation and probably also the cytokine production pattern of keratinocytes.

Biomechanics of normal and pathological gait: implications for understanding human locomotor control.

PubMed

Winter, D A

1989-12-01

The biomechanical (kinetic) analysis of human gait reveals the integrated and detailed motor patterns that are essential in pinpointing the abnormal patterns in pathological gait. In a similar manner, these motor patterns (moments, powers, and EMGs) can be used to identify synergies and to validate theories of CNS control. Based on kinetic and EMG patterns for a wide range of normal subjects and cadences, evidence is presented that both supports and negates the central pattern generator theory of locomotion. Adaptive motor patterns that are evident in peripheral gait pathologies reinforce a strong peripheral rather than a central control. Finally, a three-component subtask theory of human gait is presented and is supported by reference to the motor patterns seen in a normal gait. The identified subtasks are (a) support (against collapse during stance); (b) dynamic balance of the upper body, also during stance; and (c) feedforward control of the foot trajectory to achieve safe ground clearance and a gentle heel contact.

[Professor DONG Gui-rong's experience for the treatment of peripheral facial paralysis].

PubMed

Cao, Lian-Ying; Shen, Te-Li; Zhang, Wei; Chen, Si-Hui

2012-05-01

Professor DONG Gui-rong's theoretical principle and manipulation points for peripheral facial paralysis were introduced in details from the angels of syndrome differentiation, timing, acupoint prescription and needling methods. For the syndrome differentiation and timing, the professor emphasized to check the treatment timing and follow the symptoms, which should be treated by stages, besides, it was necessary to find and distinguish the reason and nature of diseases to have a combined treatment of tendons and muscles. For the acupoint prescription and needling methods, he has proposed that the acupoints selection should be compatible of distal and lacal, and made a best of Baihui (GV 20) to regulate the whole yang qi, also he has paid much attention to the needling methods and staging treatment. Under the consideration of late stage of peripheral facial paralysis, based on syndrome differentiation Back-shu points have been selected to regulate zang-fu function, should achieve much better therapeutic effect.

Optoacoustic angiography of peripheral vasculature

NASA Astrophysics Data System (ADS)

Ermilov, Sergey; Su, Richard; Zamora, Mario; Hernandez, Travis; Nadvoretsky, Vyacheslav; Oraevsky, Alexander

2012-02-01

We developed a new optoacoustic microangiography system (OmAS) intended for in-vivo vascular imaging of a human finger. The system employs an arc-shaped acoustic array that is rotated 360 degrees around the finger providing optoacoustic data necessary for tomographic reconstruction of the three-dimensional images of a finger. A near-infrared Q-switched laser is used to generate optoacoustic signals with increased contrast of blood vessels. The laser is coupled through two randomized fiberoptic bundles oriented in orthogonal optoacoustic mode. To demonstrate OmAS capabilities, we present a time-series of optoacoustic images of a human finger taken after the hypothermia stress test. The images show a detailed vascular anatomy of a finger down to the capillary level. A series of quick 30s scans allowed us to visualize the thermoregulatory response within the studied finger as it was manifested via vasomotor activity during the hypothermia recovery. We propose that the developed system can be used for diagnostics of various medical conditions that are manifested in change of the peripheral (finger) blood flow. Examples of the medical conditions that could be diagnosed and staged using the OmAS include the peripheral arterial disease (PAD), thrombosis, frostbite, and traumas.

Neurobiology of fibromyalgia and chronic widespread pain.

PubMed

Sluka, Kathleen A; Clauw, Daniel J

2016-12-03

Fibromyalgia is the current term for chronic widespread musculoskeletal pain for which no alternative cause can be identified. The underlying mechanisms, in both human and animal studies, for the continued pain in individuals with fibromyalgia will be explored in this review. There is a substantial amount of support for alterations of central nervous system nociceptive processing in people with fibromyalgia, and that psychological factors such as stress can enhance the pain experience. Emerging evidence has begun exploring other potential mechanisms including a peripheral nervous system component to the generation of pain and the role of systemic inflammation. We will explore the data and neurobiology related to the role of the CNS in nociceptive processing, followed by a short review of studies examining potential peripheral nervous system changes and cytokine involvement. We will not only explore the data from human subjects with fibromyalgia but will relate this to findings from animal models of fibromyalgia. We conclude that fibromyalgia and related disorders are heterogenous conditions with a complicated pathobiology with patients falling along a continuum with one end a purely peripherally driven painful condition and the other end of the continuum is when pain is purely centrally driven. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Characterization of peripheral blood human immunodeficiency virus isolates from Hispanic women with cognitive impairment

PubMed Central

Toro Nieves, Dianedis M; Plaud, Marinés; Wojna, Valerie; Skolasky, Richard; Meléndez, Loyda M

2009-01-01

Human immunodeficiency virus type 1 (HIV-1) tropism plays an important role in HIV-associated dementia. In this study, aimed at determining if the tropism and coreceptor usage of circulating viruses correlates with cognitive function, the authors isolated and characterized HIV from the peripheral blood of 21 Hispanic women using antiretroviral therapy. Macrophage tropism was determined by inoculation of HIV isolates onto monocyte-derived macrophages and lymphocyte cultures. To define coreceptor usage, the HIV isolates were inoculated onto the U87.CD4 glioma cell lines with specific CCR5 and CXCR4 coreceptors. HIV isolates from cognitively impaired patients showed higher levels of replication in mitogen-stimulated peripheral blood mononuclear cells than did isolates from patients with normal cognition (P < .05). The viral growth of HIV primary isolates in macrophages and lymphocytes did not differ between patients with and those without cognitive impairment. However, isolates from the cognitively impaired women preferentially used the X4 coreceptor (P < .05). These phenotypic studies suggest that cognitively impaired HIV-infected women receiving treatment may have a more highly replicating and more pathogenic X4 virus in the circulation that could contribute to their neuropathogenesis. PMID:17849315

Functional collagen conduits combined with human mesenchymal stem cells promote regeneration after sciatic nerve transection in dogs.

PubMed

Cui, Yi; Yao, Yao; Zhao, Yannan; Xiao, Zhifeng; Cao, Zongfu; Han, Sufang; Li, Xing; Huan, Yong; Pan, Juli; Dai, Jianwu

2018-05-01

Numerous studies have focused on the development of novel and innovative approaches for the treatment of peripheral nerve injury using artificial nerve guide conduits. In this study, we attempted to bridge 3.5-cm defects of the sciatic nerve with a longitudinally oriented collagen conduit (LOCC) loaded with human umbilical cord mesenchymal stem cells (hUC-MSCs). The LOCC contains a bundle of longitudinally aligned collagenous fibres enclosed in a hollow collagen tube. Our previous studies showed that an LOCC combined with neurotrophic factors enhances peripheral nerve regeneration. However, it remained unknown whether an LOCC seeded with hUC-MSCs could also promote regeneration. In this study, using various histological and electrophysiological analyses, we found that an LOCC provides mechanical support to newly growing nerves and functions as a structural scaffold for cells, thereby stimulating sciatic nerve regeneration. The LOCC and hUC-MSCs synergistically promoted regeneration and improved the functional recovery in a dog model of sciatic nerve injury. Therefore, the combined use of an LOCC and hUC-MSCs might have therapeutic potential for the treatment of peripheral nerve injury. Copyright © 2018 John Wiley & Sons, Ltd.

An Improved method for separation of leucocytes from peripheral blood of the little skate (Leucoraja erinacea)

PubMed Central

Tomana, Mitsuru; Parton, Angela; Barnes, David W.

2008-01-01

Cartilaginous fish, especially sharks, rays and skates (elasmobranchs) hold interest as comparative models in immunology because they are thought to be among the organisms most closely related to the ancestor animal that first developed acquired immunity. The aim of this study was to improve methods used for the purification of viable leucocytes from peripheral blood of elasmobranchs. Here we describe modifications of density gradient centrifugation and medium formulation that improve isolation and analysis of highly-purified leucocytes from peripheral blood of a model elasmobranch, Leucoraja erinacea, the little skate. These techniques contribute to the preparation of elasmobranch immune cells that can be reliably analyzed by a variety of means, including the study of immune function. PMID:18474431

Comparison of the Immulite and RIA assay methods for measuring peripheral blood progesterone levels in Greyhound bitches.

PubMed

Chapwanya, A; Clegg, T; Stanley, P; Vaughan, L

2008-09-15

Determination of optimal breeding time in bitches earmarked for single insemination only is based on measurement of peripheral blood serum or plasma progesterone concentration. In this paper a comparison is made between radioimmune assay (RIA) and chemoluminescent assay (Immulite) for determination of P4 concentrations in the bitch. The Immulite assay is shown to be an accurate and reliable method for serum or plasma P4 measurement. It compares favourably with other methods in terms of turn-around time, cost and accessibility for veterinarians in practice.

[Atherectomy for peripheral arterial disease].

PubMed

Londero, Louise Skovgaard; Høgh, Annette Langager; Lindholt, Jes Sanddal

2015-04-13

Symptomatic peripheral arterial disease is managed according to national and international guidelines and the number of vascular reconstructions performed each year has increased over the past decade mainly due to an increasing frequency of endovascular procedures. Atherectomy as an alternative to the established treatment of symptomatic peripheral arterial disease has recently been analysed in a Cochrane review. In Denmark, atherectomy is not performed and so far the evidence is poor as the method is not an alternative to the established treatment in this country.

Heat regulation: homeostasis of central temperature in man.

PubMed

Benzinger, T H

1969-10-01

Focus is on the concept of the quantitative thermostat or setpoint as it evolved experimentally, not theoretically, from measurements of central temperature at the tympanic membrane and from measurements of physiological responses by human gradient layer calorimetry and continuous analysis of oxygen consumption. Heat-flow responses as they relate to stimuli by which they are evoked -- peripheral or central temperatures at thermoreceptive sites -- and discussed, and individual systems of reflex action are described. These systems are then correlated with what is known of their tangible components -- sensory receptors, effector organs, nervous centers, and afferent or efferent nervous pathways -- classically derived from anatomical studies, lesion experiments, recording of action currents, or electrical or thermal stimulation of pertinent structures. Such as correlation is a crucial test, and when the results are consistent, they provide independent, mutual confirmation via the 2 approaches. Doubts are then removed that lesions or interferences, which are unavoidable with most neurophysiological methods, may have produced artifacts. Conversely, calorimetry allows one to observe and analyze thermoregulation in process in a human subject without disturbing normal structures or functions other than by the stresses to which the body is made to respond. Prior to a description of experimental findings, the essential methods are reviewed. With the methods of gradient layer calorimetry, tympanic (eardrum) thermonetry, and indirect calorimetry, thermoregulatory responses -- by chemical overproduction of metabolic heat -- were observed in transient states as a result of a stimulus of cold impinging on peripheral neurons or warm-inhibition removed from central structures. With tympanic thermometry permitting for the 1st time om humans the continuous recording of central thermal stimulation, and with gradient calorimetry permitting the continuous recording (with insignificant inertial distortion) of the sweating responses in precisely controlled environments of a large variety and under conditions where complete evaporation of sweat is ensured by strong but smooth air convection, a new study of physical thermoregulation was initiated in 1958. The experimental results did not support the expection that sweating would follow the average temperature of the skin in the classical tradition, with skin warm-receptors as the hypothetical origin of exciting warm-impulses and cenral temperature as a participant prescribing the action of the "thermoregulator" in some as yet undetermined, additive, manner. Vasomotor mechanisms to human thermoregulation can be assessed in quantitative manner only by whole-body calorimetry. Mechanisms of thermal homeostasis also considered include hormonal regulation, transmitter substances, conscious sensation of warmth and coordinations of behavioral and autonomic mechanisms, setpoint and its variations, and fever.

Quantitative Assessment of Foot Blood Flow by Using Dynamic Volume Perfusion CT Technique: A Feasibility Study.

PubMed

Hur, Saebeom; Jae, Hwan Jun; Jang, Yeonggul; Min, Seung-Kee; Min, Sang-Il; Lee, Dong Yeon; Seo, Sang Gyo; Kim, Hyo-Cheol; Chung, Jin Wook; Kim, Kwang Gi; Park, Eun-Ah; Lee, Whal

2016-04-01

To demonstrate the feasibility of foot blood flow measurement by using dynamic volume perfusion computed tomographic (CT) technique with the upslope method in an animal experiment and a human study. The human study was approved by the institutional review board, and written informed consent was obtained from all patients. The animal study was approved by the research animal care and use committee. A perfusion CT experiment was first performed by using rabbits. A color-coded perfusion map was reconstructed by using in-house perfusion analysis software based on the upslope method, and the measured blood flow on the map was compared with the reference standard microsphere method by using correlation analysis. A total of 17 perfusion CT sessions were then performed (a) once in five human patients and (b) twice (before and after endovascular revascularization) in six human patients. Perfusion maps of blood flow were reconstructed and analyzed. The Wilcoxon signed rank test was used to prove significant differences in blood flow before and after treatment. The animal experiment demonstrated a strong correlation (R(2) = 0.965) in blood flow between perfusion CT and the microsphere method. Perfusion maps were obtained successfully in 16 human clinical sessions (94%) with the use of 32 mL of contrast medium and an effective radiation dose of 0.31 mSv (k factor for the ankle, 0.0002). The plantar dermis showed the highest blood flow among all anatomic structures of the foot, including muscle, subcutaneous tissue, tendon, and bone. After a successful revascularization procedure, the blood flow of the plantar dermis increased by 153% (P = .031). The interpretations of the color-coded perfusion map correlated well with the clinical and angiographic findings. Perfusion CT could be used to measure foot blood flow in both animals and humans. It can be a useful modality for the diagnosis of peripheral arterial disease by providing quantitative information on foot perfusion status.

Content validity of symptom-based measures for diabetic, chemotherapy, and HIV peripheral neuropathy.

PubMed

Gewandter, Jennifer S; Burke, Laurie; Cavaletti, Guido; Dworkin, Robert H; Gibbons, Christopher; Gover, Tony D; Herrmann, David N; Mcarthur, Justin C; McDermott, Michael P; Rappaport, Bob A; Reeve, Bryce B; Russell, James W; Smith, A Gordon; Smith, Shannon M; Turk, Dennis C; Vinik, Aaron I; Freeman, Roy

2017-03-01

No treatments for axonal peripheral neuropathy are approved by the United States Food and Drug Administration (FDA). Although patient- and clinician-reported outcomes are central to evaluating neuropathy symptoms, they can be difficult to assess accurately. The inability to identify efficacious treatments for peripheral neuropathies could be due to invalid or inadequate outcome measures. This systematic review examined the content validity of symptom-based measures of diabetic peripheral neuropathy, HIV neuropathy, and chemotherapy-induced peripheral neuropathy. Use of all FDA-recommended methods to establish content validity was only reported for 2 of 18 measures. Multiple sensory and motor symptoms were included in measures for all 3 conditions; these included numbness, tingling, pain, allodynia, difficulty walking, and cramping. Autonomic symptoms were less frequently included. Given significant overlap in symptoms between neuropathy etiologies, a measure with content validity for multiple neuropathies with supplemental disease-specific modules could be of great value in the development of disease-modifying treatments for peripheral neuropathies. Muscle Nerve 55: 366-372, 2017. © 2016 Wiley Periodicals, Inc.

MRI abnormalities of peripheral nerve and muscle are common in amyotrophic lateral sclerosis and share features with multifocal motor neuropathy

PubMed Central

Staff, Nathan P.; Amrami, Kimberly K.; Howe, Benjamin M.

2015-01-01

Introduction MRI of peripheral nerve and muscle in patients with ALS may be performed to investigate alternative diagnoses including multifocal motor neuropathy (MMN). MRI findings of peripheral nerve and muscle are not well described in these conditions, making interpretation of results difficult. Methods We examined systematically the peripheral nerve and muscle MRI findings in patients with ALS (n=60) and MMN (n=8). Results In patients with ALS and MMN, abnormal MRIs were common (85% and 75%, respectively) but did not correlate with disease severity. Peripheral nerve MRI abnormalities were similar in frequency (ALS: 58% vs. MMN: 63%) with most changes being of mild-to-moderate severity. Muscle MRI changes were more common in ALS (57% vs. 33%), and no muscle atrophy was seen in patients with MMN. Discussion MRI abnormalities of peripheral nerve and muscle in ALS and MMN are common and share some features. PMID:25736373

TXNIP links redox circuitry to glucose control.

PubMed

Muoio, Deborah M

2007-06-01

Thioredoxin-interacting protein (TXNIP) binds and inhibits the reducing activity of thioredoxin. A new study (Parikh et al., 2007) implicates this redox rheostat as a negative regulator of peripheral glucose metabolism in humans. Investigators combined human physiology, genomic screening, and cell-based genetic studies to highlight TNXIP as a potential culprit in the pathogenesis of type 2 diabetes.

Outcomes from Building System Courseware for Teaching and Testing in a Discipline-Based Human Structure Curriculum

ERIC Educational Resources Information Center

Reilly, Frank D.

2011-01-01

This study investigated the educational benefits of system-based lecture notes and interactive learning objects in a peripheral nervous system component of a traditional first-year medical school human anatomy course. The impetus for the investigation was anecdotal evidence suggesting enhanced learner satisfaction with the learning resources.…

Increased cytokine production by monocytes from human subjects who consumed grape powder was not mediated by differences in dietary intake patterns

USDA-ARS?s Scientific Manuscript database

Recently, in a randomized, double-blind cross-over study, we reported that consumption of grape powder by obese human subjects increased the production of the pro-inflammatory cytokines interleukin-1' and interleukin-6 by ex vivo-derived peripheral blood monocytes after exposure to bacterial lipopol...

Peripheral Mechanisms for Vocal Production in Birds--Differences and Similarities to Human Speech and Singing

ERIC Educational Resources Information Center

Riede, Tobias; Goller, Franz

2010-01-01

Song production in songbirds is a model system for studying learned vocal behavior. As in humans, bird phonation involves three main motor systems (respiration, vocal organ and vocal tract). The avian respiratory mechanism uses pressure regulation in air sacs to ventilate a rigid lung. In songbirds sound is generated with two independently…

Automated analysis of brachial ultrasound time series

NASA Astrophysics Data System (ADS)

Liang, Weidong; Browning, Roger L.; Lauer, Ronald M.; Sonka, Milan

1998-07-01

Atherosclerosis begins in childhood with the accumulation of lipid in the intima of arteries to form fatty streaks, advances through adult life when occlusive vascular disease may result in coronary heart disease, stroke and peripheral vascular disease. Non-invasive B-mode ultrasound has been found useful in studying risk factors in the symptom-free population. Large amount of data is acquired from continuous imaging of the vessels in a large study population. A high quality brachial vessel diameter measurement method is necessary such that accurate diameters can be measured consistently in all frames in a sequence, across different observers. Though human expert has the advantage over automated computer methods in recognizing noise during diameter measurement, manual measurement suffers from inter- and intra-observer variability. It is also time-consuming. An automated measurement method is presented in this paper which utilizes quality assurance approaches to adapt to specific image features, to recognize and minimize the noise effect. Experimental results showed the method's potential for clinical usage in the epidemiological studies.

Safety of peripheral intravenous administration of vasoactive medication.

PubMed

Cardenas-Garcia, Jose; Schaub, Karen F; Belchikov, Yuly G; Narasimhan, Mangala; Koenig, Seth J; Mayo, Paul H

2015-09-01

Central venous access is commonly performed to administer vasoactive medication. The administration of vasoactive medication via peripheral intravenous access is a potential method of reducing the need for central venous access. The aim of this study was to evaluate the safety of vasoactive medication administered through peripheral intravenous access. Over a 20-month period starting in September 2012, we monitored the use of vasoactive medication via peripheral intravenous access in an 18-bed medical intensive care unit. Norepinephrine, dopamine, and phenylephrine were all approved for use through peripheral intravenous access. A total of 734 patients (age 72 ± 15 years, male/female 398/336, SAPS II score 75 ± 15) received vasoactive medication via peripheral intravenous access 783 times. Vasoactive medication used was norepinephrine (n = 506), dopamine (n = 101), and phenylephrine (n = 176). The duration of vasoactive medication via peripheral intravenous access was 49 ± 22 hours. Extravasation of the peripheral intravenous access during administration of vasoactive medication occurred in 19 patients (2%) without any tissue injury following treatment, with local phentolamine injection and application of local nitroglycerin paste. There were 95 patients (13%) receiving vasoactive medication through peripheral intravenous access who eventually required central intravenous access. Administration of norepinephrine, dopamine, or phenylephrine by peripheral intravenous access was feasible and safe in this single-center medical intensive care unit. Extravasation from the peripheral intravenous line was uncommon, and phentolamine with nitroglycerin paste were effective in preventing local ischemic injury. Clinicians should not regard the use of vasoactive medication is an automatic indication for central venous access. © 2015 Society of Hospital Medicine.

Peripheral Precocious Puberty Caused by Human Chorionic Gonadotropin Producing Pineal Gland Tumor.

PubMed

Hammadur Rahaman, S K; Khandelwal, Deepak; Khadgawat, Rajesh; Kandasamy, Devasenathipathy; Bakhshi, Sameer

2018-03-15

Pineal gland lesions usually present with central precocious puberty. A 3½-yr-old boy presented with precocious puberty. Clinically and biochemically, it was gonadotropin releasing hormone (GnRH) independent. Serum and CSF beta-hCG levels were increased. Thin section magnetic resonance imaging of brain revealed a pineal gland tumor. He received chemotherapy followed by radiotherapy and responded well. CSF beta-hCG should be measured in all cases of peripheral precocity, and if CSF beta-hCG is elevated, thin section magnetic resonance imaging of brain should be considered.

Wallerian demyelination: chronicle of a cellular cataclysm.

PubMed

Tricaud, Nicolas; Park, Hwan Tae

2017-11-01

Wallerian demyelination is characteristic of peripheral nerve degeneration after traumatic injury. After axonal degeneration, the myelinated Schwann cell undergoes a stereotypical cellular program that results in the disintegration of the myelin sheath, a process termed demyelination. In this review, we chronologically describe this program starting from the late and visible features of myelin destruction and going backward to the initial molecular steps that trigger the nuclear reprogramming few hours after injury. Wallerian demyelination is a wonderful model for myelin degeneration occurring in the diverse forms of demyelinating peripheral neuropathies that plague human beings.

Spatial-frequency cutoff requirements for pattern recognition in central and peripheral vision

PubMed Central

Kwon, MiYoung; Legge, Gordon E.

2011-01-01

It is well known that object recognition requires spatial frequencies exceeding some critical cutoff value. People with central scotomas who rely on peripheral vision have substantial difficulty with reading and face recognition. Deficiencies of pattern recognition in peripheral vision, might result in higher cutoff requirements, and may contribute to the functional problems of people with central-field loss. Here we asked about differences in spatial-cutoff requirements in central and peripheral vision for letter and face recognition. The stimuli were the 26 letters of the English alphabet and 26 celebrity faces. Each image was blurred using a low-pass filter in the spatial frequency domain. Critical cutoffs (defined as the minimum low-pass filter cutoff yielding 80% accuracy) were obtained by measuring recognition accuracy as a function of cutoff (in cycles per object). Our data showed that critical cutoffs increased from central to peripheral vision by 20% for letter recognition and by 50% for face recognition. We asked whether these differences could be accounted for by central/peripheral differences in the contrast sensitivity function (CSF). We addressed this question by implementing an ideal-observer model which incorporates empirical CSF measurements and tested the model on letter and face recognition. The success of the model indicates that central/peripheral differences in the cutoff requirements for letter and face recognition can be accounted for by the information content of the stimulus limited by the shape of the human CSF, combined with a source of internal noise and followed by an optimal decision rule. PMID:21854800

Stimulatory effect of Eucalyptus essential oil on innate cell-mediated immune response

PubMed Central

Serafino, Annalucia; Vallebona, Paola Sinibaldi; Andreola, Federica; Zonfrillo, Manuela; Mercuri, Luana; Federici, Memmo; Rasi, Guido; Garaci, Enrico; Pierimarchi, Pasquale

2008-01-01

Background Besides few data concerning the antiseptic properties against a range of microbial agents and the anti-inflammatory potential both in vitro and in vivo, little is known about the influence of Eucalyptus oil (EO) extract on the monocytic/macrophagic system, one of the primary cellular effectors of the immune response against pathogen attacks. The activities of this natural extract have mainly been recognized through clinical experience, but there have been relatively little scientific studies on its biological actions. Here we investigated whether EO extract is able to affect the phagocytic ability of human monocyte derived macrophages (MDMs) in vitro and of rat peripheral blood monocytes/granulocytes in vivo in absence or in presence of immuno-suppression induced by the chemotherapeutic agent 5-fluorouracil (5-FU). Methods Morphological activation of human MDMs was analysed by scanning electron microscopy. Phagocytic activity was tested: i) in vitro in EO treated and untreated MDMs, by confocal microscopy after fluorescent beads administration; ii) in vivo in monocytes/granulocytes from peripheral blood of immuno-competent or 5-FU immuno-suppressed rats, after EO oral administration, by flow cytometry using fluorescein-labelled E. coli. Cytokine release by MDMs was determined using the BD Cytometric Bead Array human Th1/Th2 cytokine kit. Results EO is able to induce activation of MDMs, dramatically stimulating their phagocytic response. EO-stimulated internalization is coupled to low release of pro-inflammatory cytokines and requires integrity of the microtubule network, suggesting that EO may act by means of complement receptor-mediated phagocytosis. Implementation of innate cell-mediated immune response was also observed in vivo after EO administration, mainly involving the peripheral blood monocytes/granulocytes. The 5-FU/EO combined treatment inhibited the 5-FU induced myelotoxicity and raised the phagocytic activity of the granulocytic/monocytic system, significantly decreased by the chemotherapic. Conclusion Our data, demonstrating that Eucalyptus oil extract is able to implement the innate cell-mediated immune response, provide scientific support for an additional use of this plant extract, besides those concerning its antiseptic and anti-inflammatory properties and stimulate further investigations also using single components of this essential oil. This might drive development of a possible new family of immuno-regulatory agents, useful as adjuvant in immuno-suppressive pathologies, in infectious disease and after tumour chemotherapy. PMID:18423004

The spectral sensitivity of the human short-wavelength sensitive cones derived from thresholds and color matches.

PubMed

Stockman, A; Sharpe, L T; Fach, C

1999-08-01

We used two methods to estimate short-wave (S) cone spectral sensitivity. Firstly, we measured S-cone thresholds centrally and peripherally in five trichromats, and in three blue-cone monochromats, who lack functioning middle-wave (M) and long-wave (L) cones. Secondly, we analyzed standard color-matching data. Both methods yielded equivalent results, on the basis of which we propose new S-cone spectral sensitivity functions. At short and middle-wavelengths, our measurements are consistent with the color matching data of Stiles and Burch (1955, Optica Acta, 2, 168-181; 1959, Optica Acta, 6, 1-26), and other psychophysically measured functions, such as pi 3 (Stiles, 1953, Coloquio sobre problemas opticos de la vision, 1, 65-103). At longer wavelengths, S-cone sensitivity has previously been over-estimated.

Computed aided system for separation and classification of the abnormal erythrocytes in human blood

NASA Astrophysics Data System (ADS)

Wąsowicz, Michał; Grochowski, Michał; Kulka, Marek; Mikołajczyk, Agnieszka; Ficek, Mateusz; Karpieńko, Katarzyna; Cićkiewicz, Maciej

2017-12-01

The human peripheral blood consists of cells (red cells, white cells, and platelets) suspended in plasma. In the following research the team assessed an influence of nanodiamond particles on blood elements over various periods of time. The material used in the study consisted of samples taken from ten healthy humans of various age, different blood types and both sexes. The markings were leaded by adding to the blood unmodified diamonds and oxidation modified. The blood was put under an impact of two diamond concentrations: 20μl and 100μl. The amount of abnormal cells increased with time. The percentage of echinocytes as a result of interaction with nanodiamonds in various time intervals for individual specimens was scarce. The impact of the two diamond types had no clinical importance on red blood cells. It is supposed that as a result of longlasting exposure a dehydratation of red cells takes place, because of the function of the cells. The analysis of an influence of nanodiamond particles on blood elements was supported by computer system designed for automatic counting and classification of the Red Blood Cells (RBC). The system utilizes advanced image processing methods for RBCs separation and counting and Eigenfaces method coupled with the neural networks for RBCs classification into normal and abnormal cells purposes.

Mass spectrometry profiling of oxylipins, endocannabinoids, and N-acylethanolamines in human lung lavage fluids reveals responsiveness of prostaglandin E2 and associated lipid metabolites to biodiesel exhaust exposure.

PubMed

Gouveia-Figueira, Sandra; Karimpour, Masoumeh; Bosson, Jenny A; Blomberg, Anders; Unosson, Jon; Pourazar, Jamshid; Sandström, Thomas; Behndig, Annelie F; Nording, Malin L

2017-04-01

The adverse effects of petrodiesel exhaust exposure on the cardiovascular and respiratory systems are well recognized. While biofuels such as rapeseed methyl ester (RME) biodiesel may have ecological advantages, the exhaust generated may cause adverse health effects. In the current study, we investigated the responses of bioactive lipid mediators in human airways after biodiesel exhaust exposure using lipidomic profiling methods. Lipid mediator levels in lung lavage were assessed following 1-h biodiesel exhaust (average particulate matter concentration, 159 μg/m 3 ) or filtered air exposure in 15 healthy individuals in a double-blinded, randomized, controlled, crossover study design. Bronchoscopy was performed 6 h post exposure and lung lavage fluids, i.e., bronchial wash (BW) and bronchoalveolar lavage (BAL), were sequentially collected. Mass spectrometry methods were used to detect a wide array of oxylipins (including eicosanoids), endocannabinoids, N-acylethanolamines, and related lipid metabolites in the collected BW and BAL samples. Six lipids in the human lung lavage samples were altered following biodiesel exhaust exposure, three from BAL samples and three from BW samples. Of these, elevated levels of PGE 2 , 12,13-DiHOME, and 13-HODE, all of which were found in BAL samples, reached Bonferroni-corrected significance. This is the first study in humans reporting responses of bioactive lipids following biodiesel exhaust exposure and the most pronounced responses were seen in the more peripheral and alveolar lung compartments, reflected by BAL collection. Since the responsiveness and diagnostic value of a subset of the studied lipid metabolites were established in lavage fluids, we conclude that our mass spectrometry profiling method is useful to assess effects of human exposure to vehicle exhaust.

Isolation and characterization of human umbilical cord-derived endothelial colony-forming cells

PubMed Central

Zhang, Hao; Tao, Yanling; Ren, Saisai; Liu, Haihui; Zhou, Hui; Hu, Jiangwei; Tang, Yongyong; Zhang, Bin; Chen, Hu

2017-01-01

Endothelial colony-forming cells (ECFCs) are a population of endothelial progenitor cells (EPCs) that display robust proliferative potential and vessel-forming capability. Previous studies have demonstrated that a limited number of ECFCs may be obtained from adult bone marrow, peripheral blood and umbilical cord (UC) blood. The present study describes an effective method for isolating ECFCs from human UC. The ECFCs derived from human UC displayed the full properties of EPCs. Analysis of the growth kinetics, cell cycle and colony-forming ability of the isolated human UC-ECFCs indicated that the cells demonstrated properties of stem cells, including relative stability and rapid proliferation in vitro. Gene expression of Fms related tyrosine kinase 1, kinase insert domain receptor, vascular endothelial cadherin, cluster of differentiation (CD)31, CD34, epidermal growth factor homology domains-2, von Willebrand factor and endothelial nitric oxide synthase was assessed by reverse transcription-polymerase chain reaction. The cells were positive for CD34, CD31, CD73, CD105 and vascular endothelial growth factor receptor-2, and negative for CD45, CD90 and human leukocyte antigen-antigen D related protein according to flow cytometry. 1,1′-dioctadecyl-3,3,3′,3′-tetra-methyl-indocarbocyanine perchlorate-labeled acetylated low-density lipoprotein and fluorescein isothiocyanate-Ulex europaeus-l were used to verify the identity of the UC-ECFCs. Matrigel was used to investigate tube formation capability. The results demonstrated that the reported technique is a valuable method for isolating human UC-ECFCs, which have potential for use in vascular regeneration. PMID:29067104

Noninvasive Methods for Determining Lesion Depth from Vesicant Exposure

DTIC Science & Technology

2007-01-01

LDPI. Chilcott et al19 used several noninvasive bio- a bolus through a central or peripheral venous line. engineering methods to monitor wound healing...ade- bolus through a central or peripheral venous line. The quate NBF into the tissue, two parallel cuts approxi- first two range finding pigs were...not more than 5.0%), its use creasing the size of the scan area, and/or decreasing is contraindicated in patients with a history of allergy the number

Photoacoustic imaging: a potential new tool for arthritis

NASA Astrophysics Data System (ADS)

Wang, Xueding

2012-12-01

The potential application of photoacoustic imaging (PAI) technology to diagnostic imaging and therapeutic monitoring of inflammatory arthritis has been explored. The feasibility of our bench-top joint imaging systems in delineating soft articular tissue structures in a noninvasive manner was validated first on rat models and then on human peripheral joints. Based on the study on commonly used arthritis rat models, the capability of PAI to differentiate arthritic joints from the normal was also examined. With sufficient imaging depth, PAI can realize tomographic imaging of a human peripheral joint or a small-animal joint as a whole organ noninvasively. By presenting additional optical contrast and tissue functional information such as blood volume and blood oxygen saturation, PAI may provide an opportunity for early diagnosis of inflammatory joint disorders, e.g. rheumatoid arthritis, and for monitoring of therapeutic outcomes with improved sensitivity and accuracy.

Effects of Secondary Metabolites of Permafrost Bacillus sp. on Cytokine Synthesis by Human Peripheral Blood Mononuclear Cells.

PubMed

Kalenova, L F; Kolyvanova, S S; Bazhin, A S; Besedin, I M; Mel'nikov, V P

2017-06-01

We studied the effects of secondary metabolites of Bacillus sp. isolated from late Neogene permafrost on secretion of proinflammatory (TNF-α, IL-1β, IL-8, IL-2, and IFNγ) and antiinflammatory (IL-4 and IL-10) cytokines by human peripheral blood mononuclear cells. It was found that metabolites of Bacillus sp. produced more potent effect on cytokine secretion than mitogen phytohemagglutinin and metabolites of Bacillus cereus, medicinal strain IP5832. Activity of metabolites depended on the temperature of bacteria incubation. "Cold" metabolites of Bacillus sp. (isolated at -5°C) primarily induced Th1-mediated secretion of IFNγ, while "warm" metabolites (obtained at 37°C) induced Th2-mediated secretion of IL-4. The results suggest that Bacillus sp. metabolites are promising material for the development of immunomodulating drugs.

Effect of drinking water disinfection by-products in human peripheral blood lymphocytes and sperm.

PubMed

Ali, Aftab; Kurzawa-Zegota, Malgorzata; Najafzadeh, Mojgan; Gopalan, Rajendran C; Plewa, Michael J; Anderson, Diana

2014-12-01

Drinking water disinfection by-products (DBPs) are generated by the chemical disinfection of water and may pose hazards to public health. Two major classes of DBPs are found in finished drinking water: haloacetic acids (HAAs) and trihalomethanes (THMs). HAAs are formed following disinfection with chlorine, which reacts with iodide and bromide in the water. Previously the HAAs were shown to be cytotoxic, genotoxic, mutagenic, teratogenic and carcinogenic. To determine the effect of HAAs in human somatic and germ cells and whether oxidative stress is involved in genotoxic action. In the present study both somatic and germ cells have been examined as peripheral blood lymphocytes and sperm. The effects of three HAA compounds: iodoacetic acid (IAA), bromoacetic acid (BAA) and chloroacetic acid (CAA) were investigated. After determining appropriate concentration responses, oxygen radical involvement with the antioxidants, butylated hydroxanisole (BHA) and the enzyme catalase, were investigated in the single cell gel electrophoresis (Comet) assay under alkaline conditions, >pH 13 and the micronucleus assay. In the Comet assay, BHA and catalase were able to reduce DNA damage in each cell type compared to HAA alone. In the micronucleus assay, micronuclei (MNi) were found in peripheral lymphocytes exposed to all three HAAs and catalase and BHA were in general, able to reduce MNi induction, suggesting oxygen radicals play a role in both assays. These observations are of concern to public health since both human somatic and germ cells show similar genotoxic responses. Copyright © 2014. Published by Elsevier B.V.

An alkaline comet assay study on the antimalarial drug atovaquone in human peripheral blood lymphocytes: a study based on clinically relevant concentrations.

PubMed

Dinter, Domagoj; Gajski, Goran; Garaj-Vrhovac, Vera

2013-01-01

Atovaquone, a hydroxynaphthoquinone, is an anti-parasite drug, selectively targeting the mitochondrial respiratory chain of malaria parasite. It is used for both the treatment and prevention of malaria, usually in a fixed combination with proguanil. Although atovaquone has not often been associated with severe adverse reactions in the recommended dosages and has a relatively favorable side effect profile, the present study was undertaken to evaluate its cytogenotoxic potential towards human peripheral blood lymphocytes. Two different concentrations of atovaquone found in plasma when used in fixed-dose combination with proguanile hydrochloride were used with and without S9 metabolic activation: 2950 ng ml(-1) used for prophylactic treatment and 11 800 ng ml(-1) used in treatment of malaria. The results showed that lymphocyte viability was not affected after the treatment, suggesting that atovaquone was not cytotoxic in the given concentrations. With the alkaline comet assay we demonstrated that in human peripheral blood lymphocytes no significant changes in comet parameters occurred after the treatment. There were no differences in tested parameters with the addition of S9 metabolic activation, indicating that atovaquone either has no metabolite or it is not toxic in the given concentrations. Since no effects were observed after the treatment, it is to be concluded that atovaquone is safe from the aspect of genototoxicity in the recommended dosages. Copyright © 2011 John Wiley & Sons, Ltd.

Simple and Reliable Method to Quantify the Hepatitis B Viral Load and Replicative Capacity in Liver Tissue and Blood Leukocytes

PubMed Central

Minosse, Claudia; Coen, Sabrina; Visco Comandini, Ubaldo; Lionetti, Raffaella; Montalbano, Marzia; Cerilli, Stefano; Vincenti, Donatella; Baiocchini, Andrea; Capobianchi, Maria R.; Menzo, Stefano

2016-01-01

Background A functional cure of chronic hepatitis B (CHB) is feasible, but a clear view of the intrahepatic viral dynamics in each patient is needed. Intrahepatic covalently closed circular DNA (cccDNA) is the stable form of the viral genome in infected cells, and represents the ideal marker of parenchymal colonization. Its relationships with easily accessible peripheral parameters need to be elucidated in order to avoid invasive procedures in patients. Objectives The goal of this study was to design, set up, and validate a reliable and straightforward method for the quantification of the cccDNA and total DNA of the hepatitis B virus (HBV) in a variety of clinical samples. Patients and Methods Clinical samples from a cohort of CHB patients, including liver biopsies in some, were collected for the analysis of intracellular HBV molecular markers using novel molecular assays. Results A plasmid construct, including sequences from the HBV genome and from the human gene hTERT, was generated as an isomolar multi-standard for HBV quantitation and normalization to the cellular contents. The specificity of the real-time assay for the cccDNA was assessed using Dane particles isolated on a density gradient. A comparison of liver tissue from 6 untreated and 6 treated patients showed that the treatment deeply reduced the replicative capacity (total DNA/cccDNA), but had limited impact on the parenchymal colonization. The peripheral blood mononuclear cells (PBMCs) and granulocytes from the treated and untreated patients were also analyzed. Conclusions A straightforward method for the quantification of intracellular HBV molecular parameters in clinical samples was developed and validated. The widespread use of such versatile assays could better define the prognosis of CHB, and allow a more rational approach to time-limited tailored treatment strategies. PMID:27882060

Microneurography as a tool in clinical neurophysiology to investigate peripheral neural traffic in humans.

PubMed

Mano, Tadaaki; Iwase, Satoshi; Toma, Shinobu

2006-11-01

Microneurography is a method using metal microelectrodes to investigate directly identified neural traffic in myelinated as well as unmyelinated efferent and afferent nerves leading to and coming from muscle and skin in human peripheral nerves in situ. The present paper reviews how this technique has been used in clinical neurophysiology to elucidate the neural mechanisms of autonomic regulation, motor control and sensory functions in humans under physiological and pathological conditions. Microneurography is particularly important to investigate efferent and afferent neural traffic in unmyelinated C fibers. The recording of efferent discharges in postganglionic sympathetic C efferent fibers innervating muscle and skin (muscle sympathetic nerve activity; MSNA and skin sympathetic nerve activity; SSNA) provides direct information about neural control of autonomic effector organs including blood vessels and sweat glands. Sympathetic microneurography has become a potent tool to reveal neural functions and dysfunctions concerning blood pressure control and thermoregulation. This recording has been used not only in wake conditions but also in sleep to investigate changes in sympathetic neural traffic during sleep and sleep-related events such as sleep apnea. The same recording was also successfully carried out by astronauts during spaceflight. Recordings of afferent discharges from muscle mechanoreceptors have been used to understand the mechanisms of motor control. Muscle spindle afferent information is particularly important for the control of fine precise movements. It may also play important roles to predict behavior outcomes during learning of a motor task. Recordings of discharges in myelinated afferent fibers from skin mechanoreceptors have provided not only objective information about mechanoreceptive cutaneous sensation but also the roles of these signals in fine motor control. Unmyelinated mechanoreceptive afferent discharges from hairy skin seem to be important to convey cutaneous sensation to the central structures related to emotion. Recordings of afferent discharges in thin myelinated and unmyelinated fibers from nociceptors in muscle and skin have been used to provide information concerning pain. Recordings of afferent discharges of different types of cutaneous C-nociceptors identified by marking method have become an important tool to reveal the neural mechanisms of cutaneous sensations such as an itch. No direct microneurographic evidence has been so far proved regarding the effects of sympathoexcitation on sensitization of muscle and skin sensory receptors at least in healthy humans.

Effect of limb cooling on peripheral and global oxygen consumption in neonates.

PubMed

Hassan, I A-A; Wickramasinghe, Y A; Spencer, S A

2003-03-01

To evaluate peripheral oxygen consumption (VO(2)) measurements using near infrared spectroscopy (NIRS) with arterial occlusion in healthy term neonates by studying the effect of limb cooling on peripheral and global VO(2). Twenty two healthy term neonates were studied. Peripheral VO(2) was measured by NIRS using arterial occlusion and measurement of the oxyhaemoglobin (HbO(2)) decrement slope. Global VO(2) was measured by open circuit calorimetry. Global and peripheral VO(2) was measured in each neonate before and after limb cooling. In 10 neonates, a fall in forearm temperature of 2.2 degrees C (mild cooling) decreased forearm VO(2) by 19.6% (p < 0.01). Global VO(2) did not change. In 12 neonates, a fall in forearm temperature of 4 degrees C (moderate cooling) decreased forearm VO(2) by 34.7% (p < 0.01). Global VO(2) increased by 17.6% (p < 0.05). The NIRS arterial occlusion method is able to measure changes in peripheral VO(2) induced by limb cooling. The changes are more pronounced with moderate limb cooling when a concomitant rise in global VO(2) is observed. Change in peripheral temperature must be taken into consideration in the interpretation of peripheral VO(2) measurements in neonates.

Increased numbers of FoxP3-expressing CD4+ CD25+ regulatory T cells in peripheral blood from dogs with atopic dermatitis and its correlation with disease severity.

PubMed

Hauck, Verena; Hügli, Patrick; Meli, Marina L; Rostaher, Ana; Fischer, Nina; Hofmann-Lehmann, Regina; Favrot, Claude

2016-02-01

Atopic dermatitis (AD) is a common chronic inflammatory skin disease of humans and dogs. Regulatory T cells (Tregs) are essential controllers of immune homeostasis and have been shown to play a key role in human AD, even though frequencies of Tregs in atopic human patients vary greatly. Only two studies have reported Treg numbers in the peripheral blood of dogs with canine AD (CAD). This study aimed to assess the numbers of circulating Tregs in healthy and atopic dogs, and to determine whether Treg numbers correlate with age, sex, disease severity or pre-treatment. Client-owned dogs including 14 healthy dogs and 35 dogs with CAD. Expression of Tregs in peripheral blood mononuclear cells was evaluated by flow cytometry. Tregs were phenotypically identified as T cells triple positive for CD4, CD25 and FoxP3. The percentage of circulating CD4(+)  CD25(+)  FoxP3(+) Tregs in atopic dogs was increased significantly compared to healthy dogs (mean 2.1% versus 1%, P = 0.002) and correlated with disease severity (Pruritus Scale: r = 0.48, P = 0.003; CADESI-04: r = 0.34, P = 0.044). No significant differences in age or sex were found in either group and pre-treatment had no influence on results for atopic dogs. Data suggest that, as in humans, CD4(+)  CD25(+)  FoxP3(+) Tregs may contribute to the pathogenesis of CAD as indicated by an association between Treg frequency and disease severity. Further investigation is required to improve the understanding of the role of Tregs in atopic dogs. © 2015 ESVD and ACVD.

Human trophoblasts recruited T lymphocytes and monocytes into decidua by secretion of chemokine CXCL16 and interaction with CXCR6 in the first-trimester pregnancy.

PubMed

Huang, Yu; Zhu, Xiao-Yong; Du, Mei-Rong; Li, Da-Jin

2008-02-15

During human early pregnancy, fetus-derived trophoblasts come into direct contact with maternal immune cells at the maternofetal interface. At sites of placental attachment, invasive extravillous trophoblasts encounter decidual leukocytes (DLC) that accumulate within the decidua. Because we first found chemokine CXCL16 was highly expressed in and secreted by the first-trimester human trophoblasts previously, in this study we tested the hypothesis of whether the fetal trophoblasts can direct migration of maternal T lymphocyte and monocytes into decidua by secreting CXCL16. We analyzed the transcription and translation of CXCL16 in the isolated first-trimester human trophoblast, and examined the kinetic secretion of CXCL16 in the supernatant of the primary-cultured trophoblasts. We demonstrated that the sole receptor of CXCL16, CXCR6, is preferentially expressed in T lymphocytes, NKT cells, and monocytes, hardly expressed in two subsets of NK cells from either the peripheral blood or decidua. We further demonstrated the chemotactic activity of CXCL16 in the supernatant of the primary trophoblast on the peripheral mononuclear cells and DLC. Moreover, the CXCL16/CXCR6 interaction is involved in the migration of the peripheral T lymphocytes, gammadelta T cells, and monocytes, but not NKT cells. In addition, the trophoblast-conditioned medium could enrich PBMC subsets selectively to constitute a leukocyte population with similar composition to that of DLC, which suggests that the fetus-derived trophoblasts can attract T cells, gammadelta T cells, and monocytes by producing CXCL16 and interaction with CXCR6 on these cells, leading to forming a specialized immune milieu at the maternofetal interface.

Transplantation of Human Dental Pulp-Derived Stem Cells or Differentiated Neuronal Cells from Human Dental Pulp-Derived Stem Cells Identically Enhances Regeneration of the Injured Peripheral Nerve.

PubMed

Ullah, Imran; Park, Ju-Mi; Kang, Young-Hoon; Byun, June-Ho; Kim, Dae-Geon; Kim, Joo-Heon; Kang, Dong-Ho; Rho, Gyu-Jin; Park, Bong-Wook

2017-09-01

Human dental mesenchymal stem cells isolated from the dental follicle, pulp, and root apical papilla of extracted wisdom teeth have been known to exhibit successful and potent neurogenic differentiation capacity. In particular, human dental pulp-derived stem cells (hDPSCs) stand out as the most prominent source for in vitro neuronal differentiation. In this study, to evaluate the in vivo peripheral nerve regeneration potential of hDPSCs and differentiated neuronal cells from DPSCs (DF-DPSCs), a total of 1 × 10 6 hDPSCs or DF-hDPSCs labeled with PKH26 tracking dye and supplemented with fibrin glue scaffold and collagen tubulization were transplanted into the sciatic nerve resection (5-mm gap) of rat models. At 12 weeks after cell transplantation, both hDPSC and DF-hDPSC groups showed notably increased behavioral activities and higher muscle contraction forces compared with those in the non-cell transplanted control group. In immunohistochemical analysis of regenerated nerve specimens, specific markers for angiogenesis, axonal fiber, and myelin sheath increased in both the cell transplantation groups. Pretransplanted labeled PKH26 were also distinctly detected in the regenerated nerve tissues, indicating that transplanted cells were well-preserved and differentiated into nerve cells. Furthermore, no difference was observed in the nerve regeneration potential between the hDPSC and DF-hDPSC transplanted groups. These results demonstrate that dental pulp tissue is an excellent stem cell source for nerve regeneration, and in vivo transplantation of the undifferentiated hDPSCs could exhibit sufficient and excellent peripheral nerve regeneration potential.

Validation of RNA-based molecular clonotype analysis for virus-specific CD8+ T-cells in formaldehyde-fixed specimens isolated from peripheral blood

PubMed Central

van Bockel, David; Price, David A.; Asher, Tedi E.; Venturi, Vanessa; Suzuki, Kazuo; Warton, Kristina; Davenport, Miles P.; Cooper, David A.; Douek, Daniel C.; Kelleher, Anthony D.

2007-01-01

Recent advances in the field of molecular clonotype analysis have enabled detailed repertoire characterization of viably isolated antigen-specific T cell populations directly ex vivo. However, in the absence of a biologically contained FACS facility, peripheral blood mononuclear cell (PBMC) preparations derived from patients infected with agents such as HIV must be formaldehyde fixed to inactivate the pathogen; this procedure adversely affects nucleic acid template quality. Here, we developed and validated a method to amplify and sequence mRNA species derived from formaldehyde fixed PBMC specimens. Antigen-specific CD8+ cytotoxic T-lymphocyte populations were identified with standard fluorochrome-conjugated peptide-major histocompatibility complex class I tetramers refolded around synthetic peptides representing immunodominant epitopes from HIV p24 Gag (KRWII[M/L]GLNK/HLA B*2705) and CMV pp65 (NLVPMVATV/HLA A*0201 and TPRVTGGGAM/HLA B*0702), and acquired in separate laboratories with or without fixation. In the presence of proteinase K pre-treatment, the observed antigen-specific CD8+ T-cell repertoire determined by molecular clonotype analysis was statistically no different whether derived from fixed or unfixed PBMC. However, oligo-dT recovery methods were not suitable for use with fixed tissue as significant skewing of clonotypic representation was observed. Thus, we have developed a reliable RNA-based method for molecular clonotype analysis that is compatible with formaldehyde fixation and therefore suitable for use with primary human samples isolated by FACS outside the context of a biological safety level 3 containment facility. PMID:17716684

Please Don't Move-Evaluating Motion Artifact From Peripheral Quantitative Computed Tomography Scans Using Textural Features.

PubMed

Rantalainen, Timo; Chivers, Paola; Beck, Belinda R; Robertson, Sam; Hart, Nicolas H; Nimphius, Sophia; Weeks, Benjamin K; McIntyre, Fleur; Hands, Beth; Siafarikas, Aris

Most imaging methods, including peripheral quantitative computed tomography (pQCT), are susceptible to motion artifacts particularly in fidgety pediatric populations. Methods currently used to address motion artifact include manual screening (visual inspection) and objective assessments of the scans. However, previously reported objective methods either cannot be applied on the reconstructed image or have not been tested for distal bone sites. Therefore, the purpose of the present study was to develop and validate motion artifact classifiers to quantify motion artifact in pQCT scans. Whether textural features could provide adequate motion artifact classification performance in 2 adolescent datasets with pQCT scans from tibial and radial diaphyses and epiphyses was tested. The first dataset was split into training (66% of sample) and validation (33% of sample) datasets. Visual classification was used as the ground truth. Moderate to substantial classification performance (J48 classifier, kappa coefficients from 0.57 to 0.80) was observed in the validation dataset with the novel texture-based classifier. In applying the same classifier to the second cross-sectional dataset, a slight-to-fair (κ = 0.01-0.39) classification performance was observed. Overall, this novel textural analysis-based classifier provided a moderate-to-substantial classification of motion artifact when the classifier was specifically trained for the measurement device and population. Classification based on textural features may be used to prescreen obviously acceptable and unacceptable scans, with a subsequent human-operated visual classification of any remaining scans. Copyright © 2017 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Individual radiation therapy patient whole-body phantoms for peripheral dose evaluations: method and specific software.

PubMed

Alziar, I; Bonniaud, G; Couanet, D; Ruaud, J B; Vicente, C; Giordana, G; Ben-Harrath, O; Diaz, J C; Grandjean, P; Kafrouni, H; Chavaudra, J; Lefkopoulos, D; de Vathaire, F; Diallo, I

2009-09-07

This study presents a method aimed at creating radiotherapy (RT) patient-adjustable whole-body phantoms to permit retrospective and prospective peripheral dose evaluations for enhanced patient radioprotection. Our strategy involves virtual whole-body patient models (WBPM) in different RT treatment positions for both genders and for different age groups. It includes a software tool designed to match the anatomy of the phantoms with the anatomy of the actual patients, based on the quality of patient data available. The procedure for adjusting a WBPM to patient morphology includes typical dimensions available in basic auxological tables for the French population. Adjustment is semi-automatic. Because of the complexity of the human anatomy, skilled personnel are required to validate changes made in the phantom anatomy. This research is part of a global project aimed at proposing appropriate methods and software tools capable of reconstituting the anatomy and dose evaluations in the entire body of RT patients in an adapted treatment planning system (TPS). The graphic user interface is that of a TPS adapted to obtain a comfortable working process. Such WBPM have been used to supplement patient therapy planning images, usually restricted to regions involved in treatment. Here we report, as an example, the case of a patient treated for prostate cancer whose therapy planning images were complemented by an anatomy model. Although present results are preliminary and our research is ongoing, they appear encouraging, since such patient-adjusted phantoms are crucial in the optimization of radiation protection of patients and for follow-up studies.

NOTE: Individual radiation therapy patient whole-body phantoms for peripheral dose evaluations: method and specific software

NASA Astrophysics Data System (ADS)

Alziar, I.; Bonniaud, G.; Couanet, D.; Ruaud, J. B.; Vicente, C.; Giordana, G.; Ben-Harrath, O.; Diaz, J. C.; Grandjean, P.; Kafrouni, H.; Chavaudra, J.; Lefkopoulos, D.; de Vathaire, F.; Diallo, I.

2009-09-01

This study presents a method aimed at creating radiotherapy (RT) patient-adjustable whole-body phantoms to permit retrospective and prospective peripheral dose evaluations for enhanced patient radioprotection. Our strategy involves virtual whole-body patient models (WBPM) in different RT treatment positions for both genders and for different age groups. It includes a software tool designed to match the anatomy of the phantoms with the anatomy of the actual patients, based on the quality of patient data available. The procedure for adjusting a WBPM to patient morphology includes typical dimensions available in basic auxological tables for the French population. Adjustment is semi-automatic. Because of the complexity of the human anatomy, skilled personnel are required to validate changes made in the phantom anatomy. This research is part of a global project aimed at proposing appropriate methods and software tools capable of reconstituting the anatomy and dose evaluations in the entire body of RT patients in an adapted treatment planning system (TPS). The graphic user interface is that of a TPS adapted to obtain a comfortable working process. Such WBPM have been used to supplement patient therapy planning images, usually restricted to regions involved in treatment. Here we report, as an example, the case of a patient treated for prostate cancer whose therapy planning images were complemented by an anatomy model. Although present results are preliminary and our research is ongoing, they appear encouraging, since such patient-adjusted phantoms are crucial in the optimization of radiation protection of patients and for follow-up studies.

Contrast-enhanced peripheral MRA: technique and contrast agents.

PubMed

Nielsen, Yousef W; Thomsen, Henrik S

2012-09-01

In the last decade contrast-enhanced magnetic resonance angiography (CE-MRA) has gained wide acceptance as a valuable tool in the diagnostic work-up of patients with peripheral arterial disease. This review presents current concepts in peripheral CE-MRA with emphasis on MRI technique and contrast agents. Peripheral CE-MRA is defined as an MR angiogram of the arteries from the aortic bifurcation to the feet. Advantages of CE-MRA include minimal invasiveness and lack of ionizing radiation. The basic technique employed for peripheral CE-MRA is the bolus-chase method. With this method a paramagnetic MRI contrast agent is injected intravenously and T1-weighted images are acquired in the subsequent arterial first-pass phase. In order to achieve high quality MR angiograms without interfering venous contamination or artifacts, a number of factors need to be taken into account. This includes magnetic field strength of the MRI system, receiver coil configuration, use of parallel imaging, contrast bolus timing technique, and k-space filling strategies. Furthermore, it is possible to optimize peripheral CE-MRA using venous compression techniques, hybrid scan protocols, time-resolved imaging, and steady-state MRA. Gadolinium(Gd)-based contrast agents are used for CE-MRA of the peripheral arteries. Extracellular Gd agents have a pharmacokinetic profile similar to iodinated contrast media. Accordingly, these agents are employed for first-pass MRA. Blood-pool Gd-based agents are characterized by prolonged intravascular stay, due to macromolecular structure or protein binding. These agents can be used for first-pass, as well as steady-state MRA. Some Gd-based contrast agents with low thermodynamic stability have been linked to development of nephrogenic systemic fibrosis in patients with severe renal insufficiency. Using optimized technique and a stable MRI contrast agent, peripheral CE-MRA is a safe procedure with diagnostic accuracy close to that of conventional catheter X-ray angiography.

Non-invasive peripheral nerve stimulation via focused ultrasound in vivo

NASA Astrophysics Data System (ADS)

Downs, Matthew E.; Lee, Stephen A.; Yang, Georgiana; Kim, Seaok; Wang, Qi; Konofagou, Elisa E.

2018-02-01

Focused ultrasound (FUS) has been employed on a wide range of clinical applications to safely and non-invasively achieve desired effects that have previously required invasive and lengthy procedures with conventional methods. Conventional electrical neuromodulation therapies that are applied to the peripheral nervous system (PNS) are invasive and/or non-specific. Recently, focused ultrasound has demonstrated the ability to modulate the central nervous system and ex vivo peripheral neurons. Here, for the first time, noninvasive stimulation of the sciatic nerve eliciting a physiological response in vivo is demonstrated with FUS. FUS was applied on the sciatic nerve in mice with simultaneous electromyography (EMG) on the tibialis anterior muscle. EMG signals were detected during or directly after ultrasound stimulation along with observable muscle contraction of the hind limb. Transecting the sciatic nerve downstream of FUS stimulation eliminated EMG activity during FUS stimulation. Peak-to-peak EMG response amplitudes and latency were found to be comparable to conventional electrical stimulation methods. Histology along with behavioral and thermal testing did not indicate damage to the nerve or surrounding regions. The findings presented herein demonstrate that FUS can serve as a targeted, safe and non-invasive alternative to conventional peripheral nervous system stimulation to treat peripheral neuropathic diseases in the clinic.

Whole-Mount Adult Ear Skin Imaging Reveals Defective Neuro-Vascular Branching Morphogenesis in Obese and Type 2 Diabetic Mouse Models.

PubMed

Yamazaki, Tomoko; Li, Wenling; Yang, Ling; Li, Ping; Cao, Haiming; Motegi, Sei-Ichiro; Udey, Mark C; Bernhard, Elise; Nakamura, Takahisa; Mukouyama, Yoh-Suke

2018-01-11

Obesity and type 2 diabetes are frequently associated with peripheral neuropathy. Though there are multiple methods for diagnosis and analysis of morphological changes of peripheral nerves and blood vessels, three-dimensional high-resolution imaging is necessary to appreciate the pathogenesis with an anatomically recognizable branching morphogenesis and patterning. Here we established a novel technique for whole-mount imaging of adult mouse ear skin to visualize branching morphogenesis and patterning of peripheral nerves and blood vessels. Whole-mount immunostaining of adult mouse ear skin showed that peripheral sensory and sympathetic nerves align with large-diameter blood vessels. Diet-induced obesity (DIO) mice exhibit defective vascular smooth muscle cells (VSMCs) coverage, while there is no significant change in the amount of peripheral nerves. The leptin receptor-deficient db/db mice, a severe obese and type 2 diabetic mouse model, exhibit defective VSMC coverage and a large increase in the amount of smaller-diameter nerve bundles with myelin sheath and unmyelinated nerve fibers. Interestingly, an increase in the amount of myeloid immune cells was observed in the DIO but not db/db mouse skin. These data suggest that our whole-mount imaging method enables us to investigate the neuro-vascular and neuro-immune phenotypes in the animal models of obesity and diabetes.

Plasma debrisoquin levels in the assessment of reduction of plasma homovanillic acid. The debrisoquin method.

PubMed

Riddle, M A; Jatlow, P I; Anderson, G M; Cho, S C; Hardin, M T; Cohen, D J; Leckman, J F

1989-06-01

Plasma concentrations of unconjugated homovanillic acid (pHVA) reflect both central nervous system (CNS) and peripheral dopamine metabolism. Debrisoquin sulfate (DBQ) blocks peripheral, but not CNS, production of HVA from dopamine. Administration of DBQ has been used to decrease the proportion of peripherally produced HVA in pHVA measurements, making such measurements more reflective of CNS turnover of dopamine. We studied the relationships between DBQ dose, plasma DBQ (pDBQ) levels, and changes in pHVA in a group of 21 subjects (9 normal controls and 12 with Tourette's syndrome). DBQ dose was moderately correlated with pDBQ levels (r = 0.63, p = 0.002). Subjects (n = 8) with mean pDBQ levels above 60 ng/ml had a 48% to 66% decrease in mean pHVA levels; this may reflect nearly complete inhibition of peripheral HVA production. Subjects (n = 13) with mean pDBQ levels below 55 ng/ml had decreases in pHVA levels from 10% to 58%. No debrisoquin was detected in cerebrospinal fluid samples. These data suggest that pDBQ levels above 60 ng/ml are sufficient to assure substantial inhibition of peripheral HVA production and that monitoring pDBQ levels may be useful when employing this method for studying CNS metabolism.

A novel copper-hydrogen peroxide formulation for prion decontamination.

PubMed

Solassol, Jerome; Pastore, Manuela; Crozet, Carole; Perrier, Veronique; Lehmann, Sylvain

2006-09-15

With the appearance of variant Creutzfeldt-Jakob disease (CJD) and the detection of infectious prions in the peripheral organs of persons with sporadic CJD, the development of decontamination methods that are compatible with medical equipment has become a major issue. Here, we show that a formulation of copper metal ions in combination with hydrogen peroxide dramatically reduces the level of prion protein (PrP)(Sc) (the scrapie isoform of PrP) present in homogenates of samples from prion-infected brains, including brain samples from humans with CJD. An animal bioassay confirmed the reduction in prion infectivity, indicating that this novel Cu(2+)-H(2)O(2) formulation has great potential for prion decontamination.

[Research consortium Neuroimmunology and pain in the research network musculoskeletal diseases].

PubMed

Schaible, H-G; Chang, H-D; Grässel, S; Haibel, H; Hess, A; Kamradt, T; Radbruch, A; Schett, G; Stein, C; Straub, R H

2018-05-01

The research consortium Neuroimmunology and Pain (Neuroimpa) explores the importance of the relationships between the immune system and the nervous system in musculoskeletal diseases for the generation of pain and for the course of fracture healing and arthritis. The spectrum of methods includes analyses at the single cell level, in vivo models of arthritis and fracture healing, imaging studies on brain function in animals and humans and analysis of data from patients. Proinflammatory cytokines significantly contribute to the generation of joint pain through neuronal cytokine receptors. Immune cells release opioid peptides which activate opioid receptors at peripheral nociceptors and thereby evoke hypoalgesia. The formation of new bone after fractures is significantly supported by the nervous system. The sympathetic nervous system promotes the development of immune-mediated arthritis. The studies show a significant analgesic potential of the neutralization of proinflammatory cytokines and of opioids which selectively inhibit peripheral neurons. Furthermore, they show that the modulation of neuronal mechanisms can beneficially influence the course of musculoskeletal diseases. Interventions in the interactions between the immune system and the nervous system hold a great therapeutic potential for the treatment of musculoskeletal diseases and pain.

[Comparative analysis of cytogenetic examination of control groups of subjects carried out in different Russian laboratories].

PubMed

Sevan'kaev, A V; Khvostunov, I K; Snigireva, G P; Novitskaia, N N; Antoshchina, M M; Fesenko, E V; Vorobtsova, I E; Neronova, E G; Domracheva, E V; Nugis, V Iu; Govorun, R D; Handogina, E K

2013-01-01

The incidence of unstable chromosome aberrations in peripheral blood lymphocytes from unirradiated control subjects was analyzed using cytogenetic data obtained from 9 cytogenetic laboratories located in Moscow, St.-Petersburg, Obninsk, and Dubna (Russia). The objective of this study was to estimate the level and spectrum of spontaneous chromosome aberrations in human lymphocytes. 1140 blood samples were taken from 1112 subjects (594 men and 546 women) aged 1 to 72. The total metaphase number was 466795. The uniform Giemsa method for peripheral blood lymphocyte cultures was used. After counting 466795 metaphases, 4288 chromosomal aberrations of various types were classified. The most frequent types of aberrations were acentrics and chromatid deletions. They made up 90% of the total number of aberrations. The remaining 10% were exchange aberrations. The number of chromosome exchanges (dicentrics and centric rings) was twice the number of chromatid exchanges. Overall, the portion ofcells with chromosomal or (and) chromatid aberrations was 0.89 +/- 0.01%; the frequency of acentrics was 0.29 +/- 0.01; the frequency of dicentrics was 0.046 +/- 0.003; the frequency of unstable chromosome aberrations was 0.35 +/- 0.01; and the frequency of chromatid aberrations was 0.57 +/- 0.01 per 100 cells.

Modification of Expanded NK Cells with Chimeric Antigen Receptor mRNA for Adoptive Cellular Therapy.

PubMed

Chu, Yaya; Flower, Allyson; Cairo, Mitchell S

2016-01-01

NK cells are bone marrow-derived cytotoxic lymphocytes that play a major role in the rejection of tumors and cells infected by viruses. The regulation of NK activation vs inhibition is regulated by the expression of a variety of NK receptors (NKRs) and specific NKRs' ligands expressed on their targets. However, factors limiting NK therapy include small numbers of active NK cells in unexpanded peripheral blood and lack of specific tumor targeting. Chimeric antigen receptors (CAR) usually include a single-chain Fv variable fragment from a monoclonal antibody, a transmembrane hinge region, and a signaling domain such as CD28, CD3-zeta, 4-1BB (CD137), or 2B4 (CD244) endodimers. Redirecting NK cells with a CAR will circumvent the limitations of the lack of NK targeting specificity. This chapter focuses on the methods to expand human NK cells from peripheral blood by co-culturing with feeder cells and to modify the expanded NK cells efficiently with the in vitro transcribed CAR mRNA by electroporation and to test the functionality of the CAR-modified expanded NK cells for use in adoptive cellular immunotherapy.

Mitochondrial Bioenergetics Is Altered in Fibroblasts from Patients with Sporadic Alzheimer's Disease.

PubMed

Pérez, María J; Ponce, Daniela P; Osorio-Fuentealba, Cesar; Behrens, Maria I; Quintanilla, Rodrigo A

2017-01-01

The identification of an early biomarker to diagnose Alzheimer's disease (AD) remains a challenge. Neuropathological studies in animal and AD patients have shown that mitochondrial dysfunction is a hallmark of the development of the disease. Current studies suggest the use of peripheral tissues, like skin fibroblasts as a possibility to detect the early pathological alterations present in the AD brain. In this context, we studied mitochondrial function properties (bioenergetics and morphology) in cultured fibroblasts obtained from AD, aged-match and young healthy patients. We observed that AD fibroblasts presented a significant reduction in mitochondrial length with important changes in the expression of proteins that control mitochondrial fusion. Moreover, AD fibroblasts showed a distinct alteration in proteolytic processing of OPA1, a master regulator of mitochondrial fusion, compared to control fibroblasts. Complementary to these changes AD fibroblasts showed a dysfunctional mitochondrial bioenergetics profile that differentiates these cells from aged-matched and young patient fibroblasts. Our findings suggest that the human skin fibroblasts obtained from AD patients could replicate mitochondrial impairment observed in the AD brain. These promising observations suggest that the analysis of mitochondrial bioenergetics could represent a promising strategy to develop new diagnostic methods in peripheral tissues of AD patients.

Isolation and preservation of peripheral blood mononuclear cells for analysis of islet antigen-reactive T cell responses: position statement of the T-Cell Workshop Committee of the Immunology of Diabetes Society.

PubMed

Mallone, R; Mannering, S I; Brooks-Worrell, B M; Durinovic-Belló, I; Cilio, C M; Wong, F S; Schloot, N C

2011-01-01

Autoimmune T cell responses directed against insulin-producing β cells are central to the pathogenesis of type 1 diabetes (T1D). Detection of such responses is therefore critical to provide novel biomarkers for T1D 'immune staging' and to understand the mechanisms underlying the disease. While different T cell assays are being developed for these purposes, it is important to optimize and standardize methods for processing human blood samples for these assays. To this end, we review data relevant to critical parameters in peripheral blood mononuclear cell (PBMC) isolation, (cryo)preservation, distribution and usage for detecting antigen-specific T cell responses. Based on these data, we propose recommendations on processing blood samples for T cell assays and identify gaps in knowledge that need to be addressed. These recommendations may be relevant not only for the analysis of T cell responses in autoimmune disease, but also in cancer and infectious disease, particularly in the context of clinical trials. © 2010 The Authors. Clinical and Experimental Immunology © 2010 British Society for Immunology.

Mitochondrial Bioenergetics Is Altered in Fibroblasts from Patients with Sporadic Alzheimer's Disease

PubMed Central

Pérez, María J.; Ponce, Daniela P.; Osorio-Fuentealba, Cesar; Behrens, Maria I.; Quintanilla, Rodrigo A.

2017-01-01

The identification of an early biomarker to diagnose Alzheimer's disease (AD) remains a challenge. Neuropathological studies in animal and AD patients have shown that mitochondrial dysfunction is a hallmark of the development of the disease. Current studies suggest the use of peripheral tissues, like skin fibroblasts as a possibility to detect the early pathological alterations present in the AD brain. In this context, we studied mitochondrial function properties (bioenergetics and morphology) in cultured fibroblasts obtained from AD, aged-match and young healthy patients. We observed that AD fibroblasts presented a significant reduction in mitochondrial length with important changes in the expression of proteins that control mitochondrial fusion. Moreover, AD fibroblasts showed a distinct alteration in proteolytic processing of OPA1, a master regulator of mitochondrial fusion, compared to control fibroblasts. Complementary to these changes AD fibroblasts showed a dysfunctional mitochondrial bioenergetics profile that differentiates these cells from aged-matched and young patient fibroblasts. Our findings suggest that the human skin fibroblasts obtained from AD patients could replicate mitochondrial impairment observed in the AD brain. These promising observations suggest that the analysis of mitochondrial bioenergetics could represent a promising strategy to develop new diagnostic methods in peripheral tissues of AD patients. PMID:29056898

Potential of cancer screening with serum surface-enhanced Raman spectroscopy and a support vector machine

NASA Astrophysics Data System (ADS)

Li, S. X.; Zhang, Y. J.; Zeng, Q. Y.; Li, L. F.; Guo, Z. Y.; Liu, Z. M.; Xiong, H. L.; Liu, S. H.

2014-06-01

Cancer is the most common disease to threaten human health. The ability to screen individuals with malignant tumours with only a blood sample would be greatly advantageous to early diagnosis and intervention. This study explores the possibility of discriminating between cancer patients and normal subjects with serum surface-enhanced Raman spectroscopy (SERS) and a support vector machine (SVM) through a peripheral blood sample. A total of 130 blood samples were obtained from patients with liver cancer, colonic cancer, esophageal cancer, nasopharyngeal cancer, gastric cancer, as well as 113 blood samples from normal volunteers. Several diagnostic models were built with the serum SERS spectra using SVM and principal component analysis (PCA) techniques. The results show that a diagnostic accuracy of 85.5% is acquired with a PCA algorithm, while a diagnostic accuracy of 95.8% is obtained using radial basis function (RBF), PCA-SVM methods. The results prove that a RBF kernel PCA-SVM technique is superior to PCA and conventional SVM (C-SVM) algorithms in classification serum SERS spectra. The study demonstrates that serum SERS, in combination with SVM techniques, has great potential for screening cancerous patients with any solid malignant tumour through a peripheral blood sample.

Submicroscopic placental infection by non-falciparum Plasmodium spp.

PubMed Central

Doritchamou, Justin Y. A.; Akuffo, Richard A.; Moussiliou, Azizath; Luty, Adrian J. F.; Massougbodji, Achille; Deloron, Philippe

2018-01-01

Background Among the Plasmodium species that infect humans, adverse effects of P. falciparum and P. vivax have been extensively studied and reported with respect to poor outcomes particularly in first time mothers and in pregnant women living in areas with unstable malaria transmission. Although, other non-falciparum malaria infections during pregnancy have sometimes been reported, little is known about the dynamics of these infections during pregnancy. Methods and findings Using a quantitative PCR approach, blood samples collected from Beninese pregnant women during the first antenatal visit (ANV) and at delivery including placental blood were screened for Plasmodium spp. Risk factors associated with Plasmodium spp. infection during pregnancy were assessed as well as the relationships with pregnancy outcomes. P. falciparum was the most prevalent Plasmodium species detected during pregnancy, irrespective either of parity, of age or of season during which the infection occurred. Although no P. vivax infections were detected in this cohort, P. malariae (9.2%) and P. ovale (5.8%) infections were observed in samples collected during the first ANV. These non-falciparum infections were also detected in maternal peripheral blood (1.3% for P. malariae and 1.2% for P. ovale) at delivery. Importantly, higher prevalence of P. malariae (5.5%) was observed in placental than peripheral blood while that of P. ovale was similar (1.8% in placental blood). Among the non-falciparum infected pregnant women with paired peripheral and placental samples, P. malariae infections in the placental blood was significantly higher than in the peripheral blood, suggesting a possible affinity of P. malariae for the placenta. However, no assoctiation of non-falciparum infections and the pregnancy outcomes was observed Conclusions Overall this study provided insights into the molecular epidemiology of Plasmodium spp. infection during pregnancy, indicating placental infection by non-falciparum Plasmodium and the lack of association of these infections with adverse pregnancy outcomes. PMID:29432484

Evaluation of Epidural and Peripheral Nerve Catheter Heating During Magnetic Resonance Imaging

PubMed Central

Owens, Sean; Erturk, M. Arcan; Ouanes, Jean-Pierre P.; Murphy, Jamie D.; Wu, Christopher L.; Bottomley, Paul A.

2014-01-01

Background Many epidural and peripheral nerve catheters contain conducting wire that could heat during magnetic resonance imaging (MRI), requiring removal for scanning. Methods We tested 2 each of 6 brands of regional analgesia catheters (from Arrow International, B. Braun Medical, and Smiths Medical/Portex) for exposure to clinical 1.5 and 3 Tesla (T) MRI. Catheters testing as non-magnetic were placed in an epidural configuration in a standard human torso-sized phantom, and an MRI pulse sequence applied at the maximum scanner-allowed radio frequency (RF) specific absorption rate (SAR) for 15 minutes Temperature and SAR exposure were sampled during MRI using multiple fiber-optic temperature sensors. Results Two catheters (the Arrow StimuCath Peripheral Nerve, and Braun Medical Perifix FX Epidural) were found to be magnetic and not tested further. At 3T, exposure of the remaining 3 epidural and 1 peripheral nerve catheter to the scanner’s maximum RF exposure, elicited anomalous heating of 4 to 7°C in 2 Arrow Epidural (MultiPort and Flex-Tip Plus) catheters at the entry points. Temperature increases for the other catheters at 3T and all catheters at 1.5T were ≤1.4°C. When normalized to the body-average FDA guideline SAR of 4W/kg, maximum projected temperature increases were 0.1 to 2.5°C at 1.5T and 0.7 to 2.7°C at 3T, except for the Arrow MultiPort Flex-Tip Plus catheter at 3T whose increase was 14°C. Conclusions Most but not all catheters can be left in place during 1.5T MRI scans. Heating of <3°C during MRI for most catheters is not expected to be injurious. While heating was lower at 1.5T vs 3T, performance differences between products underscore the need for safety testing before performing MRI. PMID:25275576

Brief debrisoquin administration to assess central dopaminergic function in children.

PubMed

Riddle, M A; Shaywitz, B A; Leckman, J F; Anderson, G M; Shaywitz, S E; Hardin, M T; Ort, S I; Cohen, D J

1986-03-17

Central dopaminergic (DA) function in children was assessed by monitoring plasma-free homovanillic acid (pHVA) levels after brief (18 hour) administration with debrisoquin sulfate, a peripherally active antihypertensive agent that blocks peripheral, but not central, HVA production. Brief debrisoquin administration resulted in marked reductions in pHVA in each of six patients studied. In five of the six patients, post-debrisoquin pHVA levels remained relatively stable over the six-hour period of observation. No significant cardiovascular or behavioral side effects of debrisoquin were observed. The brief debrisoquin administration method appears to be a safe, simple, and potentially valid peripheral technique for evaluating aspects of central dopaminergic function in children with neuropsychiatric disorders. Additional work is needed to further establish this method's validity and reliability.

Tissue-specific expression of human CD4 in transgenic mice.

PubMed Central

Gillespie, F P; Doros, L; Vitale, J; Blackwell, C; Gosselin, J; Snyder, B W; Wadsworth, S C

1993-01-01

The gene for the human CD4 glycoprotein, which serves as the receptor for human immunodeficiency virus type 1, along with approximately 23 kb of sequence upstream of the translational start site, was cloned. The ability of 5' flanking sequences to direct tissue-specific expression was tested in cell culture and in transgenic mice. A 5' flanking region of 6 kb was able to direct transcription of the CD4 gene in NIH 3T3 cells but did not result in detectable expression in the murine T-cell line EL4 or in four lines of transgenic mice. A larger 5' flanking region of approximately 23 kb directed high-level CD4 transcription in the murine T-cell line EL4 and in three independent lines of transgenic mice. Human CD4 expression in all tissues analyzed was tightly correlated with murine CD4 expression; the highest levels of human CD4 RNA expression were found in the thymus and spleen, with relatively low levels detected in other tissues. Expression of human CD4 protein in peripheral blood mononuclear cells was examined by flow cytometry in these transgenic animals and found to be restricted to the murine CD4+ subset of lymphocytes. Human CD4 protein, detected with an anti-human CD4 monoclonal antibody, was present on the surface of 45 to 50% of the peripheral blood mononuclear cells from all transgenic lines. Images PMID:8474453

A comparison of some organizational characteristics of the mouse central retina and the human macula.

PubMed

Volland, Stefanie; Esteve-Rudd, Julian; Hoo, Juyea; Yee, Claudine; Williams, David S

2015-01-01

Mouse models have greatly assisted our understanding of retinal degenerations. However, the mouse retina does not have a macula, leading to the question of whether the mouse is a relevant model for macular degeneration. In the present study, a quantitative comparison between the organization of the central mouse retina and the human macula was made, focusing on some structural characteristics that have been suggested to be important in predisposing the macula to stresses leading to degeneration: photoreceptor density, phagocytic load on the RPE, and the relative thinness of Bruch's membrane. Light and electron microscopy measurements from retinas of two strains of mice, together with published data on human retinas, were used for calculations and subsequent comparisons. As in the human retina, the central region of the mouse retina possesses a higher photoreceptor cell density and a thinner Bruch's membrane than in the periphery; however, the magnitudes of these periphery to center gradients are larger in the human. Of potentially greater relevance is the actual photoreceptor cell density, which is much greater in the mouse central retina than in the human macula, underlying a higher phagocytic load for the mouse RPE. Moreover, at eccentricities that correspond to the peripheral half of the human macula, the rod to cone ratio is similar between mouse and human. Hence, with respect to photoreceptor density and phagocytic load of the RPE, the central mouse retina models at least the more peripheral part of the macula, where macular degeneration is often first evident.

X-linked retinitis pigmentosa: Report of a large kindred with loss of central vision and preserved peripheral function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shastry, B.S.; Trese, M.T.

1995-11-20

X-linked retinitis pigmentosa (XLRP) is the most severe form of the inherited forms of retinitis pigmentosa and is clinically variable and genetically heterogeneous. It affects one in 20,000 live births. The affected individuals manifest degeneration of the peripheral retina during the first two decades of life on the basis of night blindness. Central vision usually is preserved until age 50, when the disease advances, affecting central vision and ultimately leading to complete loss of sight. Linkage analysis has shown two loci with a possibility of a third locus on the human X chromosome. The genetic abnormality that causes XLRP ismore » not known at present. Here we describe a large kindred which manifests central loss of field with the preservation of peripheral vision. 5 refs., 1 fig.« less

Peripheral neuropathy in HIV: prevalence and risk factors

PubMed Central

Evans, Scott R.; Ellis, Ronald J.; Chen, Huichao; Yeh, Tzu-min; Lee, Anthony J.; Schifitto, Giovanni; Wu, Kunling; Bosch, Ronald J.; McArthur, Justin C.; Simpson, David M.; Clifford, David B.

2011-01-01

Objectives To estimate neuropathic sign/symptom rates with initiation of combination antiretroviral therapy (cART) in HIV-infected ART-naive patients, and to investigate risk factors for: peripheral neuropathy and symptomatic peripheral neuropathy (SPN), recovery from peripheral neuropathy/SPN after neurotoxic ART (nART) discontinuation, and the absence of peripheral neuropathy/SPN while on nART. Design AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trial participants who initiated cART in randomized trials for ART-naive patients were annually screened for symptoms/signs of peripheral neuropathy. ART use and disease characteristics were collected longitudinally. Methods Peripheral neuropathy was defined as at least mild loss of vibration sensation in both great toes or absent/hypoactive ankle reflexes bilaterally. SPN was defined as peripheral neuropathy and bilateral symptoms. Generalized estimating equation logistic regression was used to estimate associations. Results Two thousand, one hundred and forty-one participants were followed from January 2000 to June 2007. Rates of peripheral neuropathy/SPN at 3 years were 32.1/8.6% despite 87.1% with HIV-1RNA 400 copies/ml or less and 70.3% with CD4 greater than 350 cells/µl. Associations with higher odds of peripheral neuropathy included older patient age and current nART use. Associations with higher odds of SPN included older patient age, nART use, and history of diabetes mellitus. Associations with lower odds of recovery after nART discontinuation included older patient age. Associations with higher odds of peripheral neuropathy while on nART included older patient age and current protease inhibitor use. Associations with higher odds of SPN while on nART included older patient age, history of diabetes, taller height, and protease inhibitor use. Conclusion Signs of peripheral neuropathy remain despite virologic/immunologic control but frequently occurs without symptoms. Aging is a risk factor for peripheral neuropathy/SPN. PMID:21330902

Telomeric repeat-containing RNA (TERRA) related to polycystic ovary syndrome (PCOS).

PubMed

Wang, Caiqin; Shen, Fengxian; Zhu, Yuning; Fang, Yuying; Lu, Shiming

2017-04-01

Telomeric repeat-containing RNA (TERRA) participates in the regulation of telomere length, and leucocyte telomere length (LTL) plays an important role in the pathophysiology of polycystic ovary syndrome (PCOS), but little is known about the role of TERRA in PCOS. To evaluate the role of TERRA and peripheral blood LTL in PCOS. Forty women with PCOS and 35 healthy women without PCOS were recruited. A prospective case-control study was performed. RNA fluorescence in situ hybridization (FISH) was used to detect TERRA expression in peripheral blood leucocyte. Quantitative PCR was used to measure TERRA expression and the mean LTL in the PCOS and control groups. We analysed the association between related clinical parameters and the age-adjusted ratio of the telomere repeat length (T/S ratio) or TERRA. Telomeric repeat-containing RNA was expressed in human peripheral blood leucocytes, and the signal was abolished after culture with RNase A. The age-adjusted LTLs were significantly longer in the PCOS group than in the control group (P < 0·01). The age-adjusted TERRA level was significantly lower in the PCOS group than in the control group (P < 0·01). Testosterone (TTE) was related positively to LTL and negatively to TERRA in the PCOS group (r = 0·532, P = 0·002; r = -0·477, P = 0·017). We found TERRA expression in human peripheral blood leucocytes, and LTLs were positively associated with PCOS. TERRA and testosterone play an important role in the LTL regulation in PCOS. © 2016 John Wiley & Sons Ltd.

"Ecstasy" toxicity to adolescent rats following an acute low binge dose.

PubMed

Teixeira-Gomes, Armanda; Costa, Vera Marisa; Feio-Azevedo, Rita; Duarte, José Alberto; Duarte-Araújo, Margarida; Fernandes, Eduarda; Bastos, Maria de Lourdes; Carvalho, Félix; Capela, João Paulo

2016-06-28

3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") is a worldwide drug of abuse commonly used by adolescents. Most reports focus on MDMA's neurotoxicity and use high doses in adult animals, meanwhile studies in adolescents are scarce. We aimed to assess in rats the acute MDMA toxicity to the brain and peripheral organs using a binge dose scheme that tries to simulate human adolescent abuse. Adolescent rats (postnatal day 40) received three 5 mg/kg doses of MDMA (estimated equivalent to two/three pills in a 50 kg adolescent), intraperitoneally, every 2 h, while controls received saline. After 24 h animal sacrifice took place and collection of brain areas (cerebellum, hippocampus, frontal cortex and striatum) and peripheral organs (liver, heart and kidneys) occurred. Significant hyperthermia was observed after the second and third MDMA doses, with mean increases of 1 °C as it occurs in the human scenario. MDMA promoted ATP levels fall in the frontal cortex. No brain oxidative stress-related changes were observed after MDMA. MDMA-treated rat organs revealed significant histological tissue alterations including vascular congestion, but no signs of apoptosis or necrosis were found, which was corroborated by the lack of changes in plasma biomarkers and tissue caspases. In peripheral organs, MDMA did not affect significantly protein carbonylation, glutathione, or ATP levels, but liver presented a higher vulnerability as MDMA promoted an increase in quinoprotein levels. Adolescent rats exposed to a moderate MDMA dose, presented hyperthermia and acute tissue damage to peripheral organs without signs of brain oxidative stress.

Mesenchymal stem cell and derived exosome as small RNA carrier and Immunomodulator to improve islet transplantation.

PubMed

Wen, Di; Peng, Yang; Liu, Di; Weizmann, Yossi; Mahato, Ram I

2016-09-28

Human bone marrow mesenchymal stem cells (hBMSCs) and their exosomes can suppress immune reaction and deliver small RNAs. Thus, they may improve islet transplantation by delivering small RNAs for promoting islet function and inhibiting immune rejection. Here, we proposed an hBMSC and its exosome-based therapy to overcome immune rejection and poor islet function, both of which hinder the success of islet transplantation. We found overexpressed siFas and anti-miR-375 in plasmid encoding shFas and anti-miR-375 transfected hBMSC-derived exosomes, which silenced Fas and miR-375 of human islets and improved their viability and function against inflammatory cytokines. This plasmid transfected hBMSCs downregulated Fas and miR-375 of human islets in a humanized NOD scid gamma (NSG) mouse model, whose immune reaction was inhibited by injecting hBMSC and peripheral blood mononuclear cell (PBMC) co-cultured exosomes. These exosomes suppressed immune reaction by inhibiting PBMC proliferation and enhancing regulatory T cell (Treg) function. Collectively, our studies elucidated the mechanisms of RNA delivery from hBMSCs to human islets and the immunosuppressive effect of hBMSC and peripheral blood mononuclear cell co-cultured exosomes for improving islet transplantation. Copyright © 2016 Elsevier B.V. All rights reserved.

Genotoxic evaluation of terbinafine in human lymphocytes in vitro.

PubMed

Tolomeotti, Danielle; de Castro-Prado, Marialba Avezum Alves; de Sant'Anna, Juliane Rocha; Martins, Ana Beatriz Tozzo; Della-Rosa, Valter Augusto

2015-01-01

Terbinafine is an antimycotic drug usually used against several superficial fungal infections and with a potential application in the treatment of human cancers. Since to date there are few data on the genotoxic effects of terbinafine in mammalian cells, current study evaluated the potential genotoxic of such antifungal agent in cultured human peripheral blood lymphocytes. Terbinafine was used at the peak plasma concentration (1.0 μg/ml) and in four additional concentrations higher than the human plasmatic peak (5.0 μg/ml, 25.0 μg/ml, 50.0 μg/ml and 100.0 μg/ml). Chromosomal aberrations (CA), sister chromatid exchanges (SCE), micronuclei (MN), nucleoplasmic bridges (NP) and nuclear buds (NB) were scored as genetic endpoints. In all analysis no significant differences (α = 0.05, Kruskal-Wallis test) were observed. Complementary criterion adopted to obtain the final response in cytogenetic agreed with statistical results. Therefore, results of this study showed that terbinafine neither induced CA, SCE, MN, NP and NB nor affected significantly mitotic, replication and cytokinesis-block proliferation indices in any of the tested concentrations. It may be assumed that terbinafine was not genotoxic or cytotoxic to cultured human peripheral blood lymphocytes in our experimental conditions.

Genotoxicity of monosodium glutamate.

PubMed

Ataseven, Nazmiye; Yüzbaşıoğlu, Deniz; Keskin, Ayten Çelebi; Ünal, Fatma

2016-05-01

Monosodium glutamate (MSG) is one of the most widely used flavor enhancers throughout the world. The aim of this study is to investigate the genotoxic potential of MSG by using chromosome aberrations (CAs), sister-chromatid exchanges (SCEs), cytokinesis-blocked micronucleus (CBMN), and random amplified polymorphic DNA-polimerase chain reaction (RAPD-PCR) in cultured human lymphocytes and alkaline comet assays in isolated human lymphocytes, which were incubated with six concentrations (250, 500, 1000, 2000, 4000 and 8000 μg/mL) of MSG. The result of this study indicated that MSG significantly and dose dependently increased the frequencies of CAs, SCE and MN in all treatments and times, compared with control. However, the replication (RI) and nuclear division indices (NDI) were not affected. In this paper, in vitro genotoxic effects of the MSG was also investigated on human peripheral lymphocytes by analysing the RAPD-PCR with arbitrary 10-mer primers. The changes occurring in RAPD profiles after MSG treatment include increase or decrease in band intensity and gain or loss of bands. In the comet assay, this additive caused DNA damage at all concentrations in isolated human lymphocytes after 1-h in vitro exposure. Our results demonstrate that MSG is genotoxic to the human peripheral blood lymphocytes in vitro. Copyright © 2016. Published by Elsevier Ltd.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Srinivas, L.; Shalini, V.K.

Twigs-dry leaves smoke condensate (TDS), as a source of clastogenic ROS and carcinogenic PAH, was investigated for its in vitro DNA-damaging effect in calf thymus DNA and human peripheral lymphocytes. An aqueous turmeric component--Aq.T--with an established antioxidant activity, was tested as a DNA protectant. TDS induced 13-fold damage to calf thymus DNA as judged by the emergence of a DNA damage specific, fluorescent product (em: 405 nm). Aq.T at 800 ng/microL extended 69% protection to calf thymus DNA and was comparable to the other protectants such as curcumin, BHA, vitamin E, SOD, and CAT. In human peripheral lymphocytes, TDS inducedmore » extensive DNA damage in comparison with the tumor promoter TPA, as judged by FADU. Aq.T at 300 ng/microL extended 90% protection to human lymphocyte DNA against TDS-induced damage, and was more effective than the other protectants--DABCO, D-mannitol, sodium benzoate, vitamin E (ROS quenchers), SOD, CAT (antioxidant enzymes), tannic acid, flufenamic acid, BHA, BHT, n-PG, curcumin and quercetin (antioxidants). Aq.T offered 65% protection to human lymphocyte DNA against TPA-induced damage and was comparable to SOD. The above results indicate that TDS induces substantial DNA damage in calf thymus DNA and human lymphocytes and Aq.T is an efficient protectant.« less

Infectivity of five different types of macrophages by Leishmania infantum.

PubMed

Maia, C; Rolão, N; Nunes, M; Gonçalves, L; Campino, L

2007-08-01

Leishmania are intracellular parasites that multiply as the amastigote form in the macrophages of their vertebrate hosts. Since vaccines against leishmaniases are still under development, the control of these diseases relies on prompt diagnosis and chemotherapy in infected humans as well as in dogs, which are the main reservoir of Leishmania infantum, in Mediterranean countries. To establish the macrophage type to be used as an in vitro model for antileishmanial chemotherapeutic studies, we analysed the susceptibility of human peripheral blood derived macrophages, macrophages derived from mouse bone marrow, mouse peritoneal macrophages and macrophages differentiated from cell lines U-937 and DH82 to infection by two L. infantum strains, one obtained from a human leishmanial infection and other from a canine infection. Both strains displayed comparable behaviour in their capacity of infecting the different macrophage types. Human peripheral blood macrophages and DH82 cells were less infectable by both strains. U-937, mouse peritoneal macrophages and mouse bone marrow derived macrophages are the most active cells to phagocytose the parasites. However, U-937 cell line appears to be the most useful as Leishmania infection model providing an unlimited source of homogeneous host cells with reproducibility of the results, is less time consuming, less expensive and tolerate high doses of first line drugs for human and canine visceral leishmaniasis treatment.

Human immunodeficiency virus-infected macrophages produce soluble factors that cause histological and neurochemical alterations in cultured human brains.

PubMed Central

Pulliam, L; Herndier, B G; Tang, N M; McGrath, M S

1991-01-01

We wanted to establish an in vitro human model for AIDS-associated dementia and pursue the hypothesis that this disease process may be a result of soluble factors produced by HIV-infected macrophages. Human brain aggregates were prepared from nine different brain specimens, and were treated with supernatants from in vitro HIV-infected macrophages (SI), uninfected macrophages (SU), infected T cells, or macrophage-conditioned media from four AIDS patients. Seven of nine treated brains exposed to SI showed peripheral rarefaction after 1 wk of incubation that by ultrastructural analysis showed cytoplasmic vacuolation. Aggregates from two of three brain cultures treated with SI for 3 wk became smaller, an approximately 50% decrease in size. The degree of apparent toxicity in brains exposed to patient-derived macrophage supernatants paralleled the proportion of macrophages found to be expressing HIV p24. Ultrastructural abnormalities were not observed in brains treated with supernatants from HIV-infected T cells, uninfected macrophages, or LPS-activated macrophages. Levels of five neurotransmitter amino acids were decreased in comparison to the structural amino acid leucine. These findings suggest that HIV-infected macrophages, infected both in vitro as well as derived from AIDS patients' peripheral blood, produce factors that cause reproducible histochemical, ultrastructural, and functional abnormalities in human brain aggregates. Images PMID:1671392

Quantitative analysis of peripheral vasculitis, ischemia, and vascular leakage in uveitis using ultra-widefield fluorescein angiography.

PubMed

Karampelas, Michael; Sim, Dawn A; Chu, Colin; Carreno, Ester; Keane, Pearse A; Zarranz-Ventura, Javier; Westcott, Mark; Lee, Richard W J; Pavesio, Carlos E

2015-06-01

To investigate the relationships between peripheral vasculitis, ischemia, and vascular leakage in uveitis using ultra-widefield fluorescein angiography (FA). Cross-sectional, consecutive case series. Consecutive ultra-widefield FA images were collected from 82 uveitis patients (82 eyes) in a single center. The extent of peripheral vasculitis, capillary nonperfusion, and vessel leakage were quantified. Parameters included: (1) foveal avascular zone area and macular leakage, (2) peripheral diffuse capillary leakage and ischemia, (3) peripheral vasculitis, and (4) leakage from neovascularization. Central macular thickness measurements were derived with optical coherence tomography. Main outcome measures were correlations between central and peripheral fluorangiographic changes as well as associations between visual function, ultra-widefield FA-derived metrics, and central macular thickness. Although central leakage was associated with peripheral leakage (r = 0.553, P = .001), there was no association between foveal avascular zone size and peripheral ischemia (r = 0.114, P = .324), regardless of the underlying uveitic diagnosis. Peripheral ischemia was, however, correlated to neovascularization-related leakage (r = 0.462, P = .001) and focal vasculitis (r = 0.441, P = .001). Stepwise multiple regression analysis revealed that a poor visual acuity was independently associated with foveal avascular zone size and central macular thickness (R(2)-adjusted = 0.45, P = .001). We present a large cohort of patients with uveitis imaged with ultra-widefield FA and further describe novel methods for quantification of peripheral vascular pathology, in an attempt to identify visually significant parameters. Although we observed that relationships exist between peripheral vessel leakage, vasculitis, and ischemia, it was only macular ischemia and increased macular thickness that were independently associated with a reduced visual acuity. Copyright © 2015 Elsevier Inc. All rights reserved.

Changes in respiratory control after three hours of isocapnic hypoxia in humans

PubMed Central

Mahamed, Safraaz; Cunningham, David A; Duffin, James

2003-01-01

Despite the obvious role of hypoxia in eliciting respiratory acclimatisation in humans, the function of the peripheral chemoreflex is uncertain. We investigated this uncertainty using 3 h of isocapnic hypoxia as a stimulus (end-tidal PCO2, 0.5–1.0 mmHg above eucapnia; end-tidal PO2, 50 mmHg), hypothesising that this stimulus would induce an enhancement of the peripheral chemoreflex ventilatory response to hypoxia. Current evidence conflicts as to whether this enhancement is mediated by an increase in the sensitivity or a decrease in the threshold of the peripheral chemoreflex ventilatory response to carbon dioxide. Employing a modified rebreathing technique to assess chemoreflex function, we found evidence of the latter in nine healthy volunteers (six male, three female). Testing consisted of pairs of isoxic rebreathing tests at high and low levels of oxygen, performed before, immediately after and 1 h after a 3 h isocapnic hypoxic exposure. No parameters changed significantly in the high-oxygen rebreathing tests. In the low-oxygen rebreathing tests there were no changes in non-chemoreflex ventilatory drives, or in the sensitivity to carbon dioxide, but the carbon dioxide response threshold decreased (≈1.5 mmHg) immediately after exposure, and the decrease persisted for 1 h (one-way repeated-measures ANOVA; P < 0.05). We repeated the protocol in five of the original nine volunteers, but this time exposing them to isocapnic normoxia. No trends or significant changes were observed in any of the rebreathing test parameters. These findings demonstrate that in the earliest stages of acclimatisation, there is a decrease in the threshold of the peripheral chemoreflex response to carbon dioxide, which persists for at least 1 h after the return to normoxia. We suggest that ventilatory acclimatisation to hypoxia results from this decreased threshold, reflecting an increase in the activity of the peripheral chemoreflex. PMID:12562969

Intestinal Flora Modification of Arthritis Pattern in Spondyloarthropathy.

PubMed

Rothschild, Bruce M

2015-09-01

The reactive form of spondyloarthropathy appears inducible by exposure to agents of infectious diarrhea, but do those organisms represent the tip of the iceberg, as indicated by renewed interest in gastrointestinal flora? Prevalence of spondyloarthropathy (20% of chimpanzees [Pan] and 28% of gorillas) is independent of subspecies and species, respectively. However, there are major differences in arthritis patterns, a characteristic shared with humans. Do patterns of arthritis correlate with gastrointestinal flora? Could such associated modifications be in the form of disease induction or represent protective effectors (at least against the extent of peripheral arthritis)? The skeletons of 2 chimpanzee subspecies (79 Pan troglodytes troglodytes and 26 Pan troglodytes schweinfurthii) and 2 gorilla species (99 Gorilla gorilla and 38 Gorilla beringei) adults were examined, and arthritis pattern noted. Feces of Eastern (P. schweinfurthii and G. beringei) and Western (great apes collected in their normal ranges) apes were assessed for 16S rRNA c and its character. Patterns of arthritis recognized on examination of skeletons showed geographic variation in skeletal distribution. East African apes (P. troglodytes schweinfurthii and G. beringei) had pauciarticular arthritis and frequent sacroiliac disease, whereas West African apes (P. troglodytes troglodytes and G. gorilla) had polyarticular peripheral joint disease with minimal sacroiliac involvement. DNA evidence revealed that Corynebactericeae were prominently represented in great apes with polyarticular disease, whereas Dietzia and Bifidobacterium exposure correlated with reduced peripheral joint arthritis distribution. Suggestions of a protective effect (in this case, limiting extent of peripheral arthritis, but not the disease itself) offered by these organisms are well represented by documented effects in other diseases (eg, tuberculosis) in the zoologic record. Perhaps it is this disease-modifying character that reduces the extent of the peripheral erosive disease, while increasing propensity to axial (sacroiliac) disease. A potential role for probiotic organisms in management of arthritis in humans is suggested, as has been documented for tuberculosis, gastrointestinal disorders, and food allergies.