gebhart/patrepeval huggingface dataset:
Cytokines Cause Functional and Structural Damage to Isolated Islets of Langerhans (1985)

Cytokines are soluble, antigen non-specific, non-immunoglobulin mediators produced and secreted by blood mononuclear cells interacting in the cellular immune-response. To test the possibility that cytokines participate in the autoimmune destruction of the pancreatic beta-cells leading to insulin-dependent diabetes mellitus, isolated human or rat islets of Langerhans were incubated for 7 days with cytokine-rich, cell-free supernatants of blood mononuclear cells from healthy human donors stimulated with or without purified protein derivative of tuberculin or phytohaemagglutinin. Glucose stimulated insulin-release, and contents of insulin and glucagon in islets incubated with cytokine-rich supernatants were markedly reduced. This impairment of islet function was due to a cytotoxic effect of cytokine-rich supernatants as judged by disintegration of normal light-microscopic morphology.
A simple procedure for constructing 5'-amino-terminated oligodeoxynucleotides in aqueous solution (1997)

A rapid method for the synthesis of oligodeoxynucleotides (ODNs) terminated by 5'-amino-5'-deoxythymidine is described. A 3'-phosphorylated ODN (the donor) is incubated in aqueous solution with 5'-amino- 5'-deoxythymidine in the presence of N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC), extending the donor by one residue via a phosphoramidate bond. Template- directed ligation of the extended donor and an acceptor ODN, followed by acid hydrolysis, yields the acceptor ODN extended by a single 5'-amino-5'-deoxythymidine residue at its 5'terminus.
mPEG-PLA and PLA-PEG-PLA nanoparticles as new carriers for delivery of recombinant human Growth Hormone (rhGH) (2018)

mPEG-PLA and PLA-PEG-PLA copolymeric nanoparticles with three different PLA to PEG ratios are synthesized and used for encapsulation of recombinant human Growth hormone (rhGH). The structure and composition of the synthesized copolymers were analyzed by <sup>1</sup>H NMR and GPC techniques. Moreover, morphology, encapsulation efficiency (EE), cytotoxicity, release profile and stability of the encapsulated rhGH were measured. Structural analysis of the prepared copolymers showed that they were successfully synthesized with approximately expected molecular weight and relatively low size distribution. It was also revealed that by increasing amounts of PLA/PEG ratio, EE content and size of nanoparticles were increased. Release profile evaluation of rhGH from both formulations indicated that copolymeric nanoparticles of Di-B2 and Tri-B2 exhibited the best results among the synthesized nanospheres, by having initial burst release of 17.5% and 28% and then slow and constant release of rhGH up to 65% and 77% of the encapsulated drug, respectively. Furthermore, results of HPLC, SDS-PAGE and CD analyses showed stability of rhGH during encapsulation and release from nanoparticles. Finally, the results showed that these two formulations provided safe and efficient sustained release of rhGH for more than a month and they have the potential to do further studies under in vivo conditions.
Reduced Endothelial Nitric Oxide Synthase Expression and Production in Human Atherosclerosis (1998)

In clinically relevant human atherosclerosis, eNOS protein expression and NO release are markedly reduced. This may be involved in the progression of atherosclerosis.
Structural Modification of Proteins and Peptides (2014)

Proteins and peptides are ubiquitous in every cell and thus are vital for various biological functions. In recent years, there is an extensive growth in the development of various biologicals and large molecules like proteins and peptides. Now, they are replacing the market of existing organic based pharmaceuticals. This review article intends to summarize various structural modifications that are carried out in order to alter basic properties of peptides and proteins so that their solubility, absorption, permeability and various other problems associated with their delivery can be resolved. Thus they can offer significant therapeutic potential.
Synergism among interleukin 1, interleukin 3, and interleukin 5 in the production of eosinophils from primitive hemopoietic stem cells. (1988)

The in vitro production of eosinophils from committed progenitor cells is influenced by interleukin (IL)-5 (eosinophil differentiation factor) and to a lesser extent by IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF). In primary suspension cultures of marrow cells taken from eosinophilic mice, IL-3 induced a modest stimulation of eosinophil production compared to IL-5. In contrast, IL-3 was sevenfold more effective than IL-5 in generating eosinophil progenitors (eosinophil colony-forming units (CFU-eo] from more primitive precursors present in the marrow of normal mice. Pre-incubation of marrow cells in suspension culture with IL-3, but not IL-5, increased the recovery of myeloid precursors responsive to G-CSF, GM-CSF, CSF-1, or IL-3 two- to fourfold while eosinophil progenitor cells responsive to IL-5 were increased by more than 70-fold. Similarly, pre-incubation of bone marrow cells under clonal conditions with IL-3, but not IL-5, resulted in a more than 50 fold increase in CFU-eo responsive to IL-5 over input values. Bone marrow from mice pre-treated with 5-fluorouracil is greatly depleted of progenitor cells directly responsive to IL-3 or IL-5. IL-1 which synergistically interacts with various CSF species to confer a clonogenic response by primitive stem cells present in 5-fluorouracil-treated marrow also failed to stimulate eosinophil production. A marked synergism was observed when IL-1 and IL-3 were combined in the suspension pre-culture phase with a more than sixfold recovery of CFU-eo than induced by either factor alone. Furthermore, pre-culture of 5-fluorouracil-treated marrow cells with a combination of IL-1 and IL-3 resulted in a more than 260-fold increase of CFU-eo over input numbers. These data suggest that the concatenate action of IL-1, IL-3, and IL-5 is an absolute requirement for the in vitro generation of eosinophils from primitive hemopoietic stem cells.
Interferon gamma production by natural killer (NK) cells and NK1.1+ T cells upon NKR-P1 cross-linking. (1996)

Natural killer (NK) cells play an important role in immune response by producing interferon gamma (IFN-gamma) as well as exhibiting cytotoxic function. IFN-gamma produced by NK cells has been suggested to be involved in differentiation of T helper cells. On the other hand, the NKR-P1 molecule was recently identified as one of the important NK cell receptors, and it recognizes certain kinds of oligosaccharides on target cells and triggers NK cells for cytotoxicity. In the present study, we found that NK cells produce great amounts of IFN-gamma upon cross-linking of the NKR-P1 molecule. In contrast, stimulation of NK cells with IL-2 induced proliferation without producing IFN-gamma. Similar to NK cells, NK1.1+ T cells also produced IFN-gamma upon NKR-P1 cross-linking. NK1.1+ T cells produced IFN-gamma but not interleukin 4 (IL-4) upon NKR-P1 cross-linking, whereas they secreted both IFN-gamma and IL-4 upon T cell receptor cross-linking. These results indicate that NKR-P1 is a receptor molecule on NK and NK1.1+ T cells that induces not only cytotoxicity but also IFN-gamma production. Our findings provide a new pathway for IFN-gamma production by NK and NK1.1+ T cells through NKR-P1 molecules; it may be essential for immune regulation.
Degradation Characteristics of PLLA-PGA Bone Fixation Devices (1997)

Parietal craniotomies of the mature rabbit skull were repositioned and fixed with resorbable plate and screws made of LactoSorb (Walter Lorenz Surgical, Jacksonville, FL) poly L-lactic acid (PLLA) and polyglycolic acid (PGA) in 20 mature rabbits. Changes in the resorbable devices as well as at the tissue-implant interface were evaluated at 2, 6, 9, and 12 months postoperatively. At 2 months, no change in the size of the implants was seen with a noninflammatory layer of surrounding fibrous tissue and intense birefringence of the screws. At 6 months, substantial loss of implant size had occurred, accompanied by fibrovascular and a macrophage cellular infiltrate. At 9 months, more than 95% of the implant was resorbed, with a small amount remaining in the screw hole. Other than macrophages within the remaining material, very few giant cells were seen. By 1 year, no evidence of birefringent macromolecular polymer debris could be found. No contraindications for the clinical use of this specific PLLA-PGA copolyer could be found when implanted on craniofacial bone surface.
Pharmacologic Treatment Strategies in Children with Type 2 Diabetes Mellitus (2013)

We treated 80 obese and 28 nonobese children diagnosed as having type 2 diabetes mellitus (T2DM). Among these patients, 26 obese and 23 nonobese children were assigned to pharmacologic therapies during the course of diabetes. Pharmacologic therapies were started if the HbA1c (NGSP) value exceeded 7.0% despite dietary and exercise management. For the 26 obese patients, metformin alone or in combination with an additional medication was frequently used. Only 2 patients independently received sulfonylureas (SUs) in the form of glimepiride. In addition, 9 patients were treated with basal insulin supported with oral hypoglycemic drugs (OHDs) or biphasic premix insulin. On the other hand, the 23 nonobese patients were frequently treated with insulin alone or in combination with an additional medication followed by SUs. The nonobese patients tended to require pharmacologic therapies, in particular insulin, at an earlier stage of diabetes as compared with the obese patients. New antidiabetic drugs, DPP-4 inhibitors and GLP-1 receptor agonists, seemed to exert positive effects on glycemic control without occurrence of hypoglycemic episodes in some patients regardless of the type of diabetes. These results suggest that pharmacologic treatment strategies in childhood T2DM should be tailored to individual patient characteristics.
Laryngeal cancer: an overview (2012)

Abstract The authors outline the clinical features of laryngeal cancer, explain how a diagnosis is reached and describe the implications of the various treatment modalities. Copyright © 2012 John Wiley &amp; Sons
Fibroblast growth factors (1987)

Fibroblast growth factors (FGFs) are heparin-binding protein mitogens that induce division of most cultured cells derived from embryonic mesoderm and neuroectoderm. Terminally differentiated neurons also respond in vitro by eliciting outgrowth of neurites. In vivo, FGFs have been shown to induce DNA synthesis, cell migration, blood vessel growth, and dermal wound closure. The protein and nucleic acid sequences for two different FGFs, denoted acidic and basic FGF, have been determined and recognized to be homologous. Additional genes recently have been identified that extend this protein family.
Two-photon absorption standards in the 550-1600 nm excitation wavelength range (2008)

We present absolute two-photon absorption (2PA) spectra of 15 commercial organic dyes covering an extended range of excitation wavelengths, 550-1600 nm. The 2PA is measured with an estimated accuracy +/-10% using a femtosecond fluorescence excitation method. The data are corrected for the variations of the pulse duration and the beam profile with the excitation wavelength, and are applicable as reference standards for 2PA measurements.
Role of intracellular calcium concentration and protein kinase C activation in IFN-gamma stimulation of U937 cells. (1990)

IFN-gamma enhances many monocyte functions, including oxidative metabolism and Ag presentation. IFN-gamma has been reported to increase the intracellular concentration of calcium ([Ca2+]i) and modulate protein kinase C activity in murine macrophages, but the signal transduction pathways induced by IFN-gamma in human cells and their functional significance are poorly understood. Our study examined the hypothesis that an increases in [Ca2+]i and protein kinase C activation are required for functional responses to IFN-gamma. The U937 cell line was used as a model of an IFN-gamma responsive cell. IFN-gamma caused a rapid and concentration-dependent increase in [Ca2+]i, which was partly inhibited by calcium-free medium, diltiazem, and TMB-8. IFN-gamma induced a fourfold increase in the concentration of inositol 1,4,5-trisphosphate. Induction of HLA-DR, Fc gamma R, CR3, and Mo3e Ag expression by IFN-gamma was blocked by concentrations of TMB-8 that inhibited an increase in [Ca2+]i, but not by protein kinase C inhibition by H-7 or inhibition of calmodulin with W-7. Ionomycin did not enhance Ag expression and PMA induced the expression of only the Mo3e Ag. We conclude that IFN-gamma induces antigenic expression on human U937 cells by a mechanism dependent on, but not limited to, an increase in intracellular calcium, which is likely due to inositol 1,4,5-trisphosphate generation.
A physiological role for N-methyl-D-aspartic acid and non-N-methyl-D- aspartic acid receptors in pulsatile gonadotropin secretion in the adult female rat (1994)

The present study was designed to evaluate the physiological role of excitatory amino acids (EAAs) in the pulsatile secretion of LH and FSH. Specific antagonists for N-methyl-D-aspartic acid (NMDA) receptors and kainate/quisqualate (non-NMDA) receptors were used to achieve this aim. Adult female rats (250-280 g), ovariectomized for 2 weeks, were implanted with a cannula in the third ventricle of the brain. One week later, 2-amino-5-phosphono-pentanoic acid (AP-5; 10 micrograms/rat), a specific competitive NMDA receptor antagonist; 6,7-dinitroquinoxaline-2,3-dione (DNQX; 30 nM), a selective antagonist of non-NMDA receptors; or the same volume of saline, was injected via the third ventricle to conscious and unrestrained ovariectomized animals. Blood samples were collected from indwelling jugular catheters 20 min before and after injection and at 10-min intervals for 100 min for plasma LH and FSH determinations. The results revealed that the administration of either AP-5 or DNQX significantly suppressed mean as well as trough LH levels. This suppression was accompanied by a suppression of LH pulse frequency and LH pulse amplitude. AP-5 suppressed LH pulse amplitude, through LH levels, and mean LH levels to a greater degree than DNQX. The analysis of FSH pulses showed that AP-5 inhibited mean and trough FSH levels, and this appeared to be achieved by the suppression of FSH pulse amplitude, but not frequency. DNQX, on the other hand, did not significantly alter FSH pulse frequency, pulse amplitude, or trough or mean FSH levels. Taken as a whole, the present study provides evidence that endogenous EAAs, acting through both NMDA and non-NMDA receptors, play an important physiological role in the generation of pulsatile LH secretion in adult female rats. FSH pulse frequency was not significantly affected by the administration of either EAA receptor antagonist, although AP-5 did suppress FSH pulse amplitude and mean and trough FSH levels.
Amines: synthesis, properties, and applications (2005)

Preface 1. An introduction to the amines 2. Aliphatic, fatty and cyclic amines 3. Aryl amines 4. Heterocyclic amines 5. Inorganic amines, hydrazine, hydroxylamine and amine ligands 6. Small-scale syntheses and analytical methods for amines 7. Amine protection, amine oxides and amino acids 8. Selected commercial applications of amines Appendices Index.
Induction of lysosomal and plasma membrane-bound sialidases in human T-cells via T-cell receptor (2004)

Among the three isoenzymes of neuraminidase (Neu) or sialidase, Neu-1 has been suggested to be induced by cell activation and to be involved in IL (interleukin)-4 biosynthesis in murine T-cells. In the present study, we found that antigen-induced airway eosinophilia, a typical response dependent on Th2 (T-helper cell type 2) cytokines, as well as mRNA expression of Th2 cytokines, including IL-4, are suppressed in Neu-1-deficient mice, thereby demonstrating the in vivo role of murine Neu-1 in regulation of Th2 cytokines. To elucidate the roles of various sialidases in human T-cell activation, we investigated their tissue distribution, gene induction and function. Neu-1 is the predominant isoenzyme at the mRNA level in most tissues and cells in both mice and humans, including T-cells. T-cells also have significant levels of Neu-3 mRNAs, albeit much lower than those of Neu-1, whereas the levels of Neu-2 mRNAs are minimal. In human T-cells, both Neu-1 and Neu-3 mRNAs are significantly induced by T-cell-receptor stimulation, as is sialidase activity against 4-methylumbelliferyl- N -acetylneuramic acid (a substrate for both Neu-1 and Neu-3) and the ganglioside G(D1a) [NeuAcalpha2-3Galbeta1-3GalNAcbeta1-4(NeuAcalpha2-3)Galbeta1-4Glcbeta1-cer] (a substrate for Neu-3, but not for Neu-1). The expression of the two sialidase genes may be under differential regulation. Western blot analysis and enzymic comparison with recombinant sialidases have revealed that Neu-3 is induced as a major isoform in activated cells. The induction of Neu-1 and Neu-3 in T-cells is unique. In human monocytes and neutrophils stimulated with various agents, the only observation of sialidase induction has been by IL-1 in neutrophils. Functionally, a major difference has been observed in Jurkat T-cell lines over-expressing Neu-1- and Neu-3. Upon T-cell receptor stimulation, IL-2, interferon-gamma, IL-4 and IL-13 are induced in the Neu-1 line, whereas in the Neu-3 line the same cytokines are induced, with the exception of IL-4. Taken together, these results suggest an important immunoregulatory role for both Neu-1 and Neu-3 in humans.
RNA–cytoskeletal associations (1999)

It has become evident over the past years that a large fraction of messenger RNAs is tightly associated with the cytoskeleton. Whereas microtubules are involved in RNA-cytoskeletal association in large cells like oocytes, neurons, or oligodendrocytes, microfilaments play the major role in smaller somatic cell types. Association of RNA with cytoskeletal filaments clearly is required for mRNA transport, but also appears to be crucial for efficient protein synthesis. Recent data now shed light on how mRNAs attach to the cytoskeleton. Messenger RNA seems to interact with microtubules or microfilaments in the form of large ribonucleoprotein particles, which in some cases also contain components of the protein synthesis apparatus. Recently, a number of RNA binding proteins have been identified in flies, amphibians, and mammals that are essential for the interaction of mRNA with cytoskeletal filaments or with microtubule- or actin-associated proteins. Such proteins include heterologous ribonucleoproteins, which are also involved in nuclear export of RNA.
5G cellular: key enabling technologies and research challenges (2015)

The evolving fifth generation (5G) cellular wireless networks are envisioned to provide higher data rates, enhance end-user quality-of-experience (QoE), reduce end-to-end latency, and lower energy consumption. This article presents several emerging technologies which could enable and define future 5G mobile communication standards and cellular networks. We highlight the key ideas for each technology and the major open research challenges related to measurement, testing and validating the performance of 5G system components. Then, we highlight the fundamental research challenges for resource management in 5G systems.
Upcoming Candidate Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease (2012)

Dementia due to Alzheimer's disease (AD) is estimated to reach epidemic proportions by the year 2030. Given the limited accuracy of current AD clinical diagnosis, biomarkers of AD pathologies are currently being sought. Reductions in cerebrospinal fluid levels of β-amyloid 42 (a marker of amyloid plaques) and elevations in tau species (markers of neurofibrillary tangles and/or neurodegeneration) are well-established as biomarkers useful for AD diagnosis and prognosis. However, novel markers for other features of AD pathophysiology (e.g., β-amyloid processing, neuroinflammation and neuronal stress/dysfunction) and for other non-AD dementias are required to improve the accuracy of AD disease diagnosis, prognosis, staging and therapeutic monitoring (theragnosis). This article discusses the potential of several promising novel cerebrospinal fluid analytes, highlights the next steps critical for advancement in the field, and provides a prediction on how the field may evolve in 5-10 years.
Cross talk of the interferon‐α/β signalling complex with gp130 for effective interleukin‐6 signalling (2001)

The constitutive weak IFN-alpha/beta signal provides a foundation for strong cellular responses to IL-6, IFN-gamma, and possibly other cytokines. Our results also suggest the assembly of cytokine receptor subunits, which may represent a 'receptosome'-like structure, allowing the unique signalling cross talks to occur.
Quantitative PCR Assessments of Bacterial Species in Women with and without Bacterial Vaginosis (2010)

Knowledge of the abundance of bacterial species in vaginal communities will help us to better understand their role in health and disease. However, progress in this field has been limited because quantifying bacteria in natural specimens is an arduous process. We developed quantitative real-time PCR (qPCR) assays to facilitate assessments of bacterial abundance in vaginal specimens and evaluated the utility of these assays by measuring species abundance in patients whose vaginal floras were clinically described as normal, intermediate, or bacterial vaginosis (BV) as defined by Nugent's criteria. The qPCR measurements showed that Lactobacillus species were predominant in normal vaginal specimens and that high Lactobacillus crispatus and Lactobacillus jensenii abundance was specific to normal specimens, while Lactobacillus iners abundance was high in all categories including BV. The abundances of all non-Lactobacillus species were higher in BV specimens than in normal specimens. Prevotella species were prevalent in all specimens and represented a high percentage of total species in BV specimens. qPCR assays can be a useful tool for describing the structure of vaginal communities and elucidating their role in health and disease.
Iodination of Aromatic Ethers by Use of Benzyltrimethylammonium Dichloroiodate and Zinc Chloride (1988)

Abstract The reaction of aromatic ethers with benzyltrimethylammonium dichloroiodate(1-) in acetic acid in the presence of zinc chloride at room temperature gave iodo-substituted aromatic ethers in good yields.
Therapeutic recombinant proteins: trends in US approvals 1982 to 2002. (2003)

Recombinant proteins have become an important class of therapeutics since the first product was approved for marketing in the US in 1982. To determine trends in the clinical development and approval processes for therapeutic recombinant proteins, data for 270 products that entered clinical study in the period 1980 to 2002 were collected and analyzed. Mean clinical and approval phase lengths for 54 US-approved products stratified by time period, therapeutic indication, protein type, review rating and FDA review center are compared. Approval success rates, calculated using three methods that differ only in the definition of success, and the variation of approval success rates over five time periods are presented.