gebhart/patrepeval huggingface dataset:
Aminooxyacetic Acid Results in Excitotoxin Lesions by a Novel Indirect Mechanism (1991)

Aminooxyacetic acid (AOAA) is an inhibitor of several pyridoxal phosphate-depedent enzymes in the brain. In the present experiments intrastriatal injections of AOAA produced dose-dependent excitotoxic lesions. The lesions were dependent on a pyridoxal phosphate mechanisms because pyridoxine blocked them. The lesions were blocked by the noncompetitive N-methyl-D-aspartate (NMDA) antagonist MK-801 and by coinjection of kynurenate, a result indicating an NMDA receptor-mediated excitotoxic process. Electrophysiologic studies showed that AOAA does not directly activate ligand-gated ion channels in cultured cortical or striatal neurons. Pentobarbital anesthesia attenuated the lesions. AOAA injections resulted in significant increases in lactate content and depletions of ATP levels. AOAA striatal lesions closely resemble Huntington's disease both neurochemically and histologically because they show striking sparing of NADPH-diaphorase and large neurons within the lesioned area. AOAA produces excitotoxic lesions by a novel indirect mechanism, which appears to be due to impairment of intracellular energy metabolism, secondary to its ability to block the mitochondrial malate-aspartate shunt. These results raise the possibility that a regional impairment of intracellular energy metabolism may secondarily result in excitotoxic neuronal death in chronic neurodegenerative illnesses, such as Huntington's disease.
Symbolic boundary calculus and feedback operators (1991)

The recent developments in microlocal analysis and pseudodifferential boundary calculus are well suited tools in the investigation of a large number of problems occurring in control theory for partial differential equations. We explain some of the basic ideas of a pseudodifferential model in the case of a distributed system with feedback acting on the boundary of a bounded domain in R n .
Higher plasma levels of complement C3a, C4a and C5a increase the risk of subretinal fibrosis in neovascular age-related macular degeneration (2016)

Our results suggest increased systemic complement activation in nAMD patients with CNV but not RAP and PCV. Our results also suggest that higher levels of systemic complement activation may increase the risk of subretinal fibrosis in nAMD patients.
Angiotensin II type 1 and bradykinin B2 receptors expressed in early stage epithelial cells derived from human embryonic stem cells (2007)

When human embryonic stem (hES) cells were placed into suspension culture followed by culture on BD matrigel coated plates in the presence of medium conditioned by NIH-3T3 cells, they differentiated into cells of which more than 95% stained positive for keratin 8 by day 14, demonstrating that the hES cells had committed to an epithelial lineage. Approximately 50% of the keratin 8 staining cells became positive for cytokeratin 14 after 26 days. Binding experiments supported by real time PCR showed that the expression of bradykinin B2 (BKB2) and angiotensin II type 1 (AT1) receptors accompanied this differentiation. Neither receptor was expressed in the pluripotent H9 stem cells. However, transduction of the hES cells with lentivirus containing BKB2 or AT1R cDNA resulted in ligand binding and ERK1/2 activation but not in Galphai or Galphaq coupled signaling. In the differentiated cells, both BKB2R and AT1R were expressed constitutively and effected typical Galphai and Galphaq coupled signaling characterized by the release of arachidonate, generation of inositol phosphates, and Ca(2+) mobilization. These signals were abolished by the receptor antagonists, losartan, and HOE 140. Angiotensin II and bradykinin also stimulated the phosphorylation of ERK1/2, JNK1/2, and p70S6 in the differentiated cells. Our results demonstrate that human embryonic stem cells can be differentiated effectively into the epithelial lineage and that when differentiated express functional, signaling AT1 and BKB2 receptors.
Silk Fibers Extruded Artificially from Aqueous Solutions of Regenerated Bombyx mori Silk Fibroin are Tougher than their Natural Counterparts (2008)

Regenerated silk fibers extruded from fibroin solutions are highly lustrous and have uniform diameters and circular cross-sections. They are stronger, more extensible, and tougher than natural silkworm silk. These fibers can be spun under clean, sterile, and carefully regulated conditions, and may permit direct incorporation of drugs for controlled release, being suitable for biomedical applications. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Mouse T Cell Membrane Proteins Rt6−1 and Rt6−2 Are Arginine/Protein Mono(ADPribosyl)transferases and Share Secondary Structure Motifs with ADP-ribosylating Bacterial Toxins (1996)

Mono ADP-ribosylation is a posttranslational protein modification that has been implicated in the regulation of key biological functions in bacteria as well as in animals. Recently, the first cDNAs for eucaryotic mono(ADPribosyl)transferases were cloned and found to exhibit significant sequence similarity only to one other known protein, the T cell differentiation antigen Rt6. In this paper we describe secondary structure analyses of Rt6 and related proteins and show conserved structure motifs and amino acid residues consistent with a common ancestry of these eucaryotic proteins and bacterial ADP-ribosyltransferases. Moreover, we have expressed soluble mouse Rt6-1 and Rt6-2 gene products in which C-terminal tags (FLAG-His6) replace the native glycosylphosphatidylinositol anchor signal sequences. Purified recombinant Rt6-2, but not Rt6-1, shows NAD+ glycohydrolase activity, which is inhibited by the arginine analogue agmatine. Immunoprecipitation of recombinant Rt6-1 and Rt6-2 with anti-FLAG M2 antibody followed by incubation with [32P]NAD+ leads to rapid and covalent incorporation of radioactivity into the light chain of the M2 antibody. The bound label is resistant to treatment with HgCl2 but sensitive to NH2OH, characteristic of arginine-linked ADP-ribosylation. These results demonstrate that Rt6-1 and RT6-2 possess the enzymatic activities typical for NAD+-dependent arginine/protein mono(ADPribosyl)transferases (EC 2.4.2.31). They are the first such enzymes to be molecularly characterized in the immune system.
Multilineage gene expression precedes commitment in the hemopoietic system. (1997)

We have tested the hypothesis that multipotential hemopoietic stem and progenitor cells prime several different lineage-affiliated programs of gene activity prior to unilineage commitment and differentiation. Using single cell RT-PCR we show that erythroid (beta-globin) and myeloid (myeloperoxidase) gene expression programs can be initiated by the same cell prior to exclusive commitment to the erythroid or granulocytic lineages. Furthermore, the multipotential state is characterized by the coexpression of several lineage-affiliated cytokine receptors. These data support a model of hemopoietic lineage specification in which unilineage commitment is prefaced by a "promiscuous" phase of multilineage locus activation.
Isolation, Crystal and Solution Structure Determination, and Biosynthesis of Tubulysins—Powerful Inhibitors of Tubulin Polymerization from Myxobacteria (2004)

Myxobacteria have it both ways: Whereas the epothilones stabilize the tubulin cytoskeleton and build microtubuli, tubulysins, which have now been isolated from Archangium gephyra and Angiococcus disciformis, have exactly the opposite effect. They induce the disintegration of the microtubuli, and even picomolar concentrations can cause cell death by apoptosis. Their effect on cell cultures exceeds that of the most active epothilones by 50-fold. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2004/z460147_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Temporary Disruption of the Blood–Brain Barrier by Use of Ultrasound and Microbubbles: Safety and Efficacy Evaluation in Rhesus Macaques (2012)

The blood-brain barrier (BBB) prevents entry of most drugs into the brain and is a major hurdle to the use of drugs for brain tumors and other central nervous system disorders. Work in small animals has shown that ultrasound combined with an intravenously circulating microbubble agent can temporarily permeabilize the BBB. Here, we evaluated whether this targeted drug delivery method can be applied safely, reliably, and in a controlled manner on rhesus macaques using a focused ultrasound system. We identified a clear safety window during which BBB disruption could be produced without evident tissue damage, and the acoustic pressure amplitude where the probability for BBB disruption was 50% and was found to be half of the value that would produce tissue damage. Acoustic emission measurements seem promising for predicting BBB disruption and damage. In addition, we conducted repeated BBB disruption to central visual field targets over several weeks in animals trained to conduct complex visual acuity tasks. All animals recovered from each session without behavioral deficits, visual deficits, or loss in visual acuity. Together, our findings show that BBB disruption can be reliably and repeatedly produced without evident histologic or functional damage in a clinically relevant animal model using a clinical device. These results therefore support clinical testing of this noninvasive-targeted drug delivery method.
A New Method for Determining the Local Environment and Orientation of Individual Side Chains of Membrane-Binding Peptides (2004)

We studied here the binding of the mastoparan X peptide to a zwitterionic lipid bilayer (POPC) and demonstrated that nitrile-derivatized amino acids can be used to determine the hydration state (or change in hydration state) of specific sites of membrane-interactive peptides (upon binding). We have also shown that polarized ATR-FTIR measurements can further be used to uncover information regarding the spatial orientation of individual side chains as well as their conformational preference within the lipid bilayer.
Breast Cancer Lung Metastasis Requires Expression of Chemokine Receptor CCR4 and Regulatory T Cells (2009)

Cancer metastasis is a leading cause of cancer morbidity and mortality. More needs to be learned about mechanisms that control this process. In particular, the role of chemokine receptors in metastasis remains controversial. Here, using a highly metastatic breast cancer (4T1) model, we show that lung metastasis is a feature of only a proportion of the tumor cells that express CCR4. Moreover, the primary tumor growing in mammary pads activates remotely the expression of TARC/CCL17 and MDC/CCL22 in the lungs. These chemokines acting through CCR4 attract both tumor and immune cells. However, CCR4-mediated chemotaxis was not sufficient to produce metastasis, as tumor cells in the lung were efficiently eliminated by natural killer (NK) cells. Lung metastasis required CCR4(+) regulatory T cells (Treg), which directly killed NK cells using beta-galactoside-binding protein. Thus, strategies that abrogate any part of this process should improve the outcome through activation of effector cells and prevention of tumor cell migration. We confirm this prediction by killing CCR4(+) cells through delivery of TARC-fused toxins or depleting Tregs and preventing lung metastasis.
Field-emitter arrays for vacuum microelectronics (1991)

An ongoing program on microfabricated field-emitter arrays has produced a gated field-emitter tip structure with submicrometer dimensions and techniques for fabricating emitter arrays with tip packaging densities of up to 1.5*10/sup 7/ tips/cm/sup 2/. Arrays have been fabricated over areas varying from a few micrometers up to 13 cm in diameter. Very small overall emitter size, materials selection, and rigorous emitter-tip processing procedures have contributed to reducing the potential required for field emission to tens of volts. Emission current densities of up to 100 A/cm/sup 2/ have been achieved with small arrays of tips, and 100-mA total emission is commonly produced with arrays 1 mm in diameter containing 10000 tips. Transconductances of 5.0 mu S per tip have been demonstrated, indicating that 50 S/cm/sup 2/ should be achievable with tip densities of 10/sup 7/ tips/cm/sup 2/. Details of the cathode arrays and a variety of performance characteristics are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
l-Methionine Production by Methionine Analog-resistant Mutants OfCorynebacterium glutamicum (1975)

Journal Article l-Methionine Production by Methionine Analog-resistant Mutants Of Corynebacterium glutamicum Hiroshi Kase, Hiroshi Kase Tokyo Research Laboratory, Kyowa Hakko Kogyo Co., Ltd., Machida-shi, Tokyo Search for other works by this author on: Oxford Academic Google Scholar Kiyoshi Nakayama Kiyoshi Nakayama Tokyo Research Laboratory, Kyowa Hakko Kogyo Co., Ltd., Machida-shi, Tokyo Search for other works by this author on: Oxford Academic Google Scholar Agricultural and Biological Chemistry, Volume 39, Issue 1, 1 January 1975, Pages 153–160, https://doi.org/10.1080/00021369.1975.10861582 Published: 01 January 1975 Article history Received: 22 July 1974 Published: 01 January 1975
Cerebral bioimaging of Cu, Fe, Zn, and Mn in the MPTP mouse model of Parkinson’s disease using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) (2009)

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been established as a powerful technique for the determination of metal and nonmetal distributions within biological systems with high sensitivity. An imaging LA-ICP-MS technique for Fe, Cu, Zn, and Mn was developed to produce large series of quantitative element maps in native brain sections of mice subchronically intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP) as a model of Parkinson's disease. Images were calibrated using matrix-matched laboratory standards. A software solution allowing a precise delineation of anatomical structures was implemented. Coronal brain sections were analyzed crossing the striatum and the substantia nigra, respectively. Animals sacrificed 2 h, 7 d, or 28 d after the last MPTP injection and controls were investigated. We observed significant decreases of Cu concentrations in the periventricular zone and the fascia dentata at 2 h and 7d and a recovery or overcompensation at 28 d, most pronounced in the rostral periventricular zone (+40%). In the cortex Cu decreased slightly to -10%. Fe increased in the interpeduncular nucleus (+40%) but not in the substantia nigra. This pattern is in line with a differential regulation of periventricular and parenchymal Cu, and with the histochemical localization of Fe, and congruent to regions of preferential MPTP binding described in the rodent brain. The LA-ICP-MS technique yielded valid and statistically robust results in the present study on 39 slices from 19 animals. Our findings underline the value of routine micro-local analytical techniques in the life sciences and affirm a role of Cu availability in Parkinson's disease.
Chemotaxis of monocytes and neutrophils to platelet-derived growth factor. (1982)

The platelet-derived growth factor (PDGF) is shown to be chemotactic for monocytes and neutrophils. Maximum monocyte chemotaxis to PDGF is fully equal to that achieved with C5a and occurs at congruent to 20 ng/ml (congruent to 0.7 nM). Maximum neutrophil chemotaxis is congruent to 60% that achieved with C5A but occurs at congruent to 1 ng/ml (congruent to 32 pM). The chemotactic activity of PDGF is blocked by specific antisera to PDGF and by protamine sulfate, a competitive inhibitor of PDGF binding to cell surfaces. In contrast to PDGF, epidermal growth factor shows no chemotactic activity for inflammatory cells at 0.5-100 ng/ml. The high level of chemotactic activity of PDGF suggests that in addition to its role as a mitogen for smooth muscle cells and fibroblasts, PDGF may be involved in attracting inflammatory cells to sites of platelet release.
Implantation of Spheramine Ã¢ in advanced Parkinson's disease (PD) (2004)

Evaluation of the safety and efficacy of unilateral stereotactic implantation of cultured human retinal pigment epithelial (hRPE) cells attached to microcarriers (Spheramine) in patients with advanced PD in an open label pilot study. Six patients with advanced PD (3 males; 3 females; mean age 52.2 years; mean duration of PD 10.2 years; mean Hoehn and Yahr stage "off" 3.75) were assessed at baseline and post-operatively using the modified CAPIT. Each patient underwent MRI-guided stereotactic transplantation of 325,000 hRPE cells attached to microcarriers in 5 tracts, 5 mm apart in the post-commissural putamen contralateral to the most affected side. Immunosuppression was not used. The UPDRS Motor (UPDR-M) score in the practically defined "off" state was the primary outcome measure. At 6 months post-op, the mean UPDRS-M (off) score improved to 35 (34%) from a pre-op baseline mean of 52 (p <.001). Secondary outcome measures improved including the total UPDRS (33%), Timed Motor Tests (on, 14%; off, 23%), PDQ39 QOL (30%), and Schwab and England score (on, 11%; off, 30%). Bilateral improvements have been observed in motor symptoms, with the greatest effect seen contralateral to the implants. Three of six patients currently have lower Dyskinesia Rating Scale scores than at baseline, while the scores of the other three are unchanged from baseline values. No "off-state" dyskinesias have been observed. Thus Spheramine implantation therapy appears to be safe and well tolerated for 6 months post-implantation.
CD8 T Cell-Mediated Killing of Cryptococcus neoformans Requires Granulysin and Is Dependent on CD4 T Cells and IL-15 (2002)

Granulysin is located in the acidic granules of cytotoxic T cells. Although the purified protein has antimicrobial activity against a broad spectrum of microbial pathogens, direct evidence for granulysin-mediated cytotoxicity has heretofore been lacking. Studies were performed to examine the regulation and activity of granulysin expressed by CD8 T cells using Cryptococcus neoformans, which is one of the most common opportunistic pathogens of AIDS patients. IL-15-activated CD8 T cells acquired anticryptococcal activity, which correlated with the up-regulation of granulysin. When granules containing granulysin were depleted using SrCl(2,) or when the gene was silenced using 21-nt small interfering RNA duplexes, the antifungal effect of CD8 T cells was abrogated. Concanamycin A and EGTA did not affect the antifungal effect, suggesting that the activity of granulysin was perforin independent. Following stimulation by the C. neoformans mitogen, CD8 T cells expressed granulysin and acquired antifungal activity. This activity required CD4 T cells and was dependent upon accessory cells. Furthermore, IL-15 was both necessary and sufficient for granulysin up-regulation in CD8 T cells. These observations are most consistent with a mechanism whereby C. neoformans mitogen is presented to CD4 T cells, which in turn activate accessory cells. The resultant IL-15 activates CD8 T cells to express granulysin, which is responsible for antifungal activity.
Systemic inflammatory response syndrome without systemic inflammation in acutely ill patients admitted to hospital in a medical emergency (1999)

Criteria of the systemic inflammatory response syndrome (SIRS) are known to include patients without systemic inflammation. Our aim was to explore additional markers of inflammation that would distinguish SIRS patients with systemic inflammation from patients without inflammation. The study included 100 acutely ill patients with SIRS. Peripheral blood neutrophil and monocyte CD11b expression, serum interleukin-6, interleukin-1beta, tumour necrosis factor-alpha and C-reactive protein were determined, and severity of inflammation was evaluated by systemic inflammation composite score based on CD11b expression, C-reactive protein and cytokine levels. Levels of CD11b expression, C-reactive protein and interleukin-6 were higher in sepsis patients than in SIRS patients who met two criteria (SIRS2 group) or three criteria of SIRS (SIRS3 group). The systemic inflammation composite score of SIRS2 patients (median 1.5; range 0-8, n=56) was lower than that of SIRS3 patients (3.5; range 0-9, n=14, P=0.013) and that of sepsis patients (5.0; range 3-10, n=19, P<0.001). The systemic inflammation composite score was 0 in 13/94 patients. In 81 patients in whom systemic inflammation composite scores exceeded 1, interleukin-6 was increased in 64 (79.0%), C-reactive protein in 59 (72.8%) and CD11b in 50 (61.7%). None of these markers, when used alone, identified all patients but at least one marker was positive in each patient. Quantifying phagocyte CD11b expression and serum interleukin-6 and C-reactive protein concurrently provides a means to discriminate SIRS patients with systemic inflammation from patients without systemic inflammation.
An in vitro limiting-dilution assay of long-term repopulating hematopoietic stem cells in the mouse (1989)

We have developed a limiting-dilution assay of long-term repopulating hematopoietic stem cells in the mouse using a miniturized stroma- dependent bone marrow culture assay in vitro. The cells were overlaid on irradiated stromal layers in microtiter wells in a range of concentrations, and frequencies of cobblestone area-forming cells (CAFC) were calculated by employing Poisson statistics. The production of secondary granulocyte/macrophage colony-forming units (CFU-G/M) in the adherent layer of individual wells was correlated with the presence of such cobblestone areas. CAFC frequencies were determined in bone marrow cell suspensions that were either enriched for marrow repopulating ability (MRA) in vivo, while depleted for spleen colony- forming units (CFU-S), or vice versa. The separation of bone marrow cells (BMC) was either based on centrifugal elutriation, or monoclonal antibody-mediated magnetic depletion of cells carrying cell surface differentiation antigens, and subsequent sorting on the basis of light scatter and rhodamine-123 retention as a measure of mitochondrial activity. In addition, 5-fluorouracil-resistant BMC were studied. Our investigations show that a time-dependent cobblestone area formation exists that reflects the turnover time and primitiveness of CAFC. The frequency of precursors forming cobblestone areas on day 28 after overlay is proposed to be a measure for MRA, whereas the day-7 CAFC frequency closely corresponds with day-12 CFU-S numbers in the suspensions tested.