gebhart/patrepeval huggingface dataset:
Generalized crystal-storing histiocytosis associated with monoclonal gammopathy: molecular analysis of a disorder with rapid clinical course and review of the literature (2002)

Crystal-storing histiocytosis (CSH) is a rare event in disorders associated with monoclonal gammopathy. The intracellular crystal formation is almost always accompanied by the expression of kappa light chains. However, the exact mechanism for the storage has not been clarified until now. We report a case of generalized CSH in a 73-year-old man who presented with IgA kappa paraproteinemia and paraproteinuria. The initially observed CSH in the bone marrow biopsy was associated with the clinical and pathomorphologic features of a monoclonal gammopathy of undetermined significance. The progression of disease could not be affected by steroid therapy and the patient died of septic shock 7 months after detection of CSH. At the time of autopsy there was evidence for multiple myeloma and generalized CSH. Two-dimensional gel electrophoresis of liver tissue combined with immunoblotting revealed the massive storage of heavy chains of alpha type and light chains of kappa type, each in a monoclonal pattern. Analysis of the stored kappa light chain by nanoelectrospray-ionization mass spectrometry indicated that it belongs to the variable (kappa)I variability subgroup. We identified some unusual amino acid substitutions including Leu59, usually important for hydrophobic interactions within a protein, at a position where it has never been previously described in plasma cell disorders. In conclusion, we present the first case of CSH with molecular identification of the stored kappa subgroup and detection of unusual amino acid substitutions. Our results suggest that conformational alterations induced by amino acid exchanges represent a crucial pathogenic factor in CSH.
Bioengineering of the skin : skin surface imaging and analysis (1997)

Anatomy of the Skin Surface. HARDWARE AND MEASURING PRINCIPLES. A: Image Analysis. The Laser-Scanning Confocal Microscope. D-Squame Adhesive Discs. Kawai's Method/Nitrocellulose Replica Method. The SkinVisiometer-A Photometric Device for theMeasurement of Skin Surface. Scanning Electron Microscopy. Analysis of Pigmentation of Human Skin (UV-Light Images). Polarized Light Photography of Human Skin. Use of Sebutape Assessed by Image Analysis to Measure Sebaceous Gland Activity. Image Analysisof Cyanoacrylate Follicular Biopsies. B: Profilometry. Laser Profilometry. Characterization of the Skin Surface by ISO-Parameters for Microtopography. GENERAL ASPECTS. Filter Mechanisms in the Description of Surface Topography. Tribology and the SkinSurface. Size and Shape of Corneocytes: Variation with Anatomic Site and Age. Comparison of Image Analysis with Profilometry. Comparative Studies of Scanning Electron Microscopy and Transmission Electron Microscopy. CLINICAL AND EXPERIMENTAL APPLICATIONS.Morphometry in Clinical Dermatology. Measurement of Human Hair Growth. Atopic Dermatitis and Other Skin Diseases. Skin Irritation: Objective Characterization in a Clinical Perspective. Dry Skin (Xerosis): Clinical Scoring and InstrumentalCharacterization. Differentiation between Nevocellular Nevi and Malignant Melanoma by Skin Roughness Parameters. PRODUCT TESTING. Effects of Detergents. Evaluation of Moisturizers. Assessment of Visual Signs of Skin Aging. Skin Atrophy Caused byCorticosteroids. INDEX.NTI/Sales CopyShelving GuideCategoriesDermatologySubcategoryBiomedical EngineeringAudienceo Cosmetic chemists and researcherso Dermatologistso Biomedical engineerso Skin pharmacologistso Radiologistso Biologists involved with skin and hairo Pharmaceutical researcherso University and medical school libraries/bookstoresContact Editor: P.P.
Varicella-Zoster Virus-Specific Immunity after Herpes Zoster (1991)

The frequency of varicella-zoster virus (VZV)-specific T lymphocytes was higher in elderly subjects who had herpes zoster infections than in age-matched controls. This increase in T cell response persisted for at least 2 years while antibody levels to VZV returned to control values at this time. There were no differences in T cell or antibody responses to VZV between individuals with and without postherpetic neuralgia. Elderly subjects who had not had herpes zoster had a comparable increase in VZV-specific T responder cell frequency after immunization with Oka strain VZV. The data suggest that the potential for a boost in T cell response to VZV persists in the elderly, and that immunization can elicit a T cell response in this age group.
Hypoxia-induced VEGF and collagen I expressions are associated with angiogenesis and fibrogenesis in experimental cirrhosis (2002)

Cirrhosis consists of hepatocyte nodules surrounded by a highly vascularized fibrous tissue. We previously showed that the development of biliary cirrhosis in the rat is associated with the occurrence of hepatocellular hypoxia and the induction of hepatic angiogenesis. We herein examined the occurrence of hypoxia in an experimental model of diethylnitrosamine (DEN)-induced cirrhosis. We also determined whether hypoxia directly affects the expression of vascular endothelial growth factor (VEGF), of VEGF receptors (Flt-1, Flk-1), and of type I and type IV collagens in activated hepatic stellate cells (HSCs) and the expression of VEGF in hepatocytes. Our results show that in DEN-treated rats, although the progression of liver fibrosis is associated with hepatocellular hypoxia and angiogenesis, VEGF and Flt-1 expressions in the liver are increased and correlated with the density of microvessels. In vitro, hypoxia induces the expression of VEGF, Flt-1, and type I collagen in activated HSCs and that of VEGF in hepatocytes. In addition, we show that hypoxia-induced type I collagen expression in HSCs may occur independently of transforming growth factor beta1 (TGF-beta1) overexpression. In conclusion, the present study provides further evidence that hepatocellular hypoxia and angiogenesis progress together with fibrogenesis after liver injury and that hypoxia directly contributes to the progression of liver fibrosis.
Reactivating Fetal Hemoglobin Expression in Human Adult Erythroblasts Through BCL11A Knockdown Using Targeted Endonucleases (2016)

We examined the efficiency, specificity, and mutational signatures of zinc finger nucleases (ZFNs), transcriptional activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 systems designed to target the gene encoding the transcriptional repressor BCL11A, in human K562 cells and human CD34<sup>+</sup> progenitor cells. ZFNs and TALENs were delivered as in vitro transcribed mRNA through electroporation; CRISPR/Cas9 was codelivered by Cas9 mRNA with plasmid-encoded guideRNA (gRNA) (pU6.g1) or in vitro transcribed gRNA (gR.1). Analyses of efficacy revealed that for these specific reagents and the delivery methods used, the ZFNs gave rise to more allelic disruption in the targeted locus compared to the TALENs and CRISPR/Cas9, which was associated with increased levels of fetal hemoglobin in erythroid cells produced in vitro from nuclease-treated CD34<sup>+</sup> cells. Genome-wide analysis to evaluate the specificity of the nucleases revealed high specificity of this specific ZFN to the target site, while specific TALENs and CRISPRs evaluated showed off-target cleavage activity. ZFN gene-edited CD34<sup>+</sup> cells had the capacity to engraft in NOD-Prkdc<sup>SCID</sup>-IL2Rγ<sup>null</sup> mice, while retaining multi-lineage potential, in contrast to TALEN gene-edited CD34<sup>+</sup> cells. CRISPR engraftment levels mirrored the increased relative plasmid-mediated toxicity of pU6.g1/Cas9 in hematopoietic stem/progenitor cells (HSPCs), highlighting the value for the further improvements of CRISPR/Cas9 delivery in primary human HSPCs.
Enhanced selectivity of oxytocin antagonists containing sarcosine in position 7 (1994)

Neurohypophyseal hormone analogues containing sarcosine (Sar) in position 7 were prepared to design more potent and selective oxytocin antagonists. The three analogues (1-3) of [Sar7]arginine-vasopressin ([Sar7]AVP) and six analogues (4-9) of [Sar7]arginine-vasotocin ([Sar7]AVT) had a reduced affinity for antidiuretic V2 receptors. The [Sar7]AVP derivatives (1-3) were potent antiuterotonic (in vitro pA2 = 7.5-8.4, in vivo 6.6-7.1) and antipressor (pA2 = 7.2-8.0) agents. The [Sar7]AVT analogues (4-9) were more potent and selective uterotonic antagonists (in vitro pA2 = 7.9-8.6, in vivo 7.1-7.5); their antipressor potencies were reduced (pA2 = 6.4-7.7). The change of the antagonistic potencies was paralleled by a change in the receptor affinities. Among other antiuterotonic analogues, [Mca1, D-Phe2, Sar7]AVT (4, Mca = beta-mercapto- beta,beta-cyclopentamethyl-enepropionic acid) and [Mca1, D-Tyr(OEt)2,Sar7]AVT (6) were synthesized, two highly potent antiuterotonic compounds (in vitro pA2 = 8.3, in vivo 7.4 and 7.5, respectively) with reduced antipressor activity (pA2 = 6.4) and reduced binding affinity to V2 receptors (Kd = 421 and 35 nM, respectively) and no anti-antidiuretic effect. Another potent antiuterotonic analogue, [Mca1,D-Trp2,-Sar7]AVT (9, in vitro pA2 = 7.9, in vivo 7.5) has virtually no binding capability to V2 receptors (Kd approximately 0.3 mM). These analogues should lead to the design of even more potent and selective oxytocin antagonists.
Innate immune responses to B. burgdorferi mediated by JNK1 and the cochaperone, methylation controlled DNAJ (MCJ) (2022)

The infections agent of Lyme disease, Borrelia Burgdorferi is a complex microorganism with a highly diverse genome. One of the most remarkable aspects of the <em>B. burgdorferi</em> genome is the large number of sequences encoding predicted or known lipoproteins, including outer-surface proteins. The <em>B. burgdorferi</em> genome encodes no recognizable toxins. Instead, this extracellular pathogen causes pathology by migration through tissues, adhesion to host cells, and evasion of immune clearance. Inflammation elicited by infection with <em>B. burgdorferi</em> depends on the ability of the spirochete to survive in the mammalian host, as well as the immune response that arises upon the interaction of the bacterium with phagocytic, T and other cell types. Innate immune responses are critical in recognition and clearance of pathogens, and also play an important role in the outcome of adaptive immune responses. The regulation of innate immune responses to pathogens occurs through the interaction of Toll-like receptors (TLRs) with pathogen-associated molecular patterns (PAMPs) and the activation of several signaling pathways whose contribution to the overall innate immune response to pathogens is poorly understood. In this study we demonstrate a mechanism of control of murine macrophage responses mediated by TLR1/2 heterodimers through c-Jun N-terminal kinase 1 (JNK1) activity. JNK also controls tumor necrosis factor production and TLR-mediated macrophage responses to <em>B. burgdorferi</em>. We also show that the proximal promoter region of the human tlr1 gene contains an AP-1 binding site that is subjected to regulation by the kinase and binds two complexes that involve the JNK substrates c-Jun, JunD, and ATF-2. These results demonstrate that JNK1 regulates the response to TLR1/2 ligands and suggest a positive feedback loop that may serve to increase the innate immune response to the spirochete. MCJ is a newly identified member of the DnaJ protein family of cochaperones that contains unique features different than the normally described DnaJ proteins. However, there is little known about its function and the role it plays in different cells and systems. It has been previously shown that MCJ is required for the repression of the ABCB1 drug transporter expression in breast cancer cells, and that this repression is mediated through the control of c-Jun protein stability. We were therefore interested in determining the role that MCJ plays in macrophages in response to <em>B. burgdorferi</em> antigens. We now provide evidence that MCJ controls inflammatory responses of macrophages through the regulation of c-Jun protein stability, and the expression and release of the inflammatory cytokine TNF through the regulation of the expression of TNF converting enzyme (TACE) inhibitor tissue inhibitor of metalloproteinase 3 (TIMP-3).
Development of Magnetic Nanostructured Silica-Based Materials as Potential Vectors for Drug-Delivery Applications (2006)

Metallic iron nanoparticles were synthesized within micron-sized mesoporous molecular sieves (with 2.9-nm pores) and hollow silica microcapsules (pores of 2.7 and 15 nm) using several cycles of wet impregnation under vacuum, followed by drying, oxidation, and reduction steps. For iron-loaded MCM-48, SQUID measurements revealed ferromagnetic behavior at room temperature with a magnetic moment as high as 3.40 emu/g (measured at 2 T) after four deposition cycles. Iron-loaded hollow silica microcapsules (250-nm wall thickness) showed a magnetic moment of 2.40 emu/g (at 2 T) after three deposition cycles and a coercivity as low as 12.9 Oe.
The retinoblastoma gene functions as a growth and tumor suppressor in human bladder carcinoma cells. (1991)

The product of the human retinoblastoma gene (RB) is a nuclear phosphoprotein that is thought to function as a tumor suppressor. Mutations of RB frequently occur in human bladder carcinoma. To investigate the significance of the functional loss of this gene in bladder cancer, an RB expression plasmid (pBARB) under control of the human beta-actin promoter was transfected into the bladder carcinoma cell line HTB9, which lacks RB expression. Marker-selected transfectants that expressed RB protein were identified by immunoblotting and immunohistochemical staining. In selected clones, stable RB expression has persisted over 1 yr under standard culture conditions with 10% serum. However, RB expression caused major alterations of HTB9 growth properties both in vitro and in vivo. RB+ transfectants lacked the ability to form colonies in semi-solid medium, and their growth rate was significantly decreased in 3% serum. In addition, the tumorigenicity of these transfectants was markedly decreased. Tumors that formed in nude mice were much smaller and had a longer latency period but were indistinguishable microscopically from those produced by parental cells. Slower growing tumors were RB+, as measured by nuclear staining of their RB protein and by a normal RB protein pattern on immunoblots. These findings support the concept that the RB gene acts as both a growth and tumor suppressor in bladder cancer cells.
The Application of Intracavernous Injection of Vasoactive Medications for Erection in Men with Spinal Cord Injury (1987)

Obtaining and sustaining an erection that is firm enough and adequate for vaginal penetration and satisfactory completion of intercourse are common problems for the male spinal cord injury patient. Intracavernous injection of vasoactive substances offers a new treatment option but it must be approached with caution in this population. During the last year we placed 20 spinal cord injury men (16 paraplegics and 4 quadriplegics) on self-injection of papaverine alone or with phentolamine. Of the patients 19 were able to obtain an erection adequate for penetration. The patient who did not obtain an adequate erection had anomalous penile venous drainage. Six episodes of priapism occurred in 3 patients: 1 had a surgical shunt placed elsewhere before he entered our program, and 2 were treated with aspiration of the corpora and injection of epinephrine. All 3 patients subsequently have been able to obtain satisfactory erections with use of lower doses of papaverine alone.
On thein Vitroandin VivoActivity of a New Synthetic Hexapeptide that Acts on the Pituitary to Specifically Release Growth Hormone* (1984)

His-DTrp-Ala-Trp-DPhe-LysNH2, [His1,Lys6] GHRP, is a new synthetic hexapeptide which specifically elicits a dosage-related release of GH in vitro and in vivo without a concomitant release of LH, FSH, TSH, or PRL and, in limited in vivo studies, insulin or glucagon. Our results indicate that this small peptide has the attributes of a hypophysiotropic hormone. In vitro the minimum and maximum active dosages ranged from 1-10 ng/ml in the pituitary incubate assay. It was active in rats, monkeys, lambs, calves, and under special experimental conditions chicks, indicating its lack of species dependency. It was active when administered iv, sc, or ip to rats. After iv injection, GH levels rose within 2 min, peaked at +10-20 min, and by 2 h usually had returned to normal. It was not possible to directly compare the potencies of [His1,Lys6]GHRP, and the GH-releasing factors GHRF-44 and GHRF-40 after a single sc injection in rats because the time course of the GH response of these peptides was different. The GH response of [His1,Lys6]GHRP was longer in duration than either of these larger peptides. Both SRIF-14 and SRIF-28 inhibited the GH response of the hexapeptide; however, SRIF-28 was about four times more active than SRIF-14 in vitro and 7.5 times more active in vivo. When this small peptide was administered sc once or twice daily to immature rats for 9 or 25 days, the BW gain increased above the control. At the end of the weight gain studies the pituitary remained fully responsive to the peptide. Thus, [His1,Lys6] GHRP may be a valuable peptide for investigating the function of the pituitary somatotrophs and, in addition, it has the potential for increasing BW gain of a variety of normal animals by inducing GH release via a direct pituitary site of action.
Combining immunological and androgen-directed approaches (2012)

The abundance of new treatment options for men with advanced prostate cancer will challenge the role of immunotherapy in these patients. Future progress may rely on optimal combination and sequencing of various immunotherapies with androgen-directed approaches as well as with other standard prostate cancer therapies, an effort which is now just beginning.
High performance wireless Ethernet (2001)

This article considers the IEEE 802.11b standard for high-performance wireless Ethernet and a proposed extension that provides for 22 Mb/s transmission. The IEEE 802.11 sets standards for wireless Ethernet or wireless local area networks. The article describes the history of the IEEE 802.11 standards and the market opportunities in the wireless Ethernet field. The article gives a brief description of the media access control layer and then presents details about the physical layer methods, including coding descriptions and performance evaluations. The article also discusses the role and limitations of spread spectrum communications in wireless Ethernet.
Conditional Random Fields as Recurrent Neural Networks (2015)

Pixel-level labelling tasks, such as semantic segmentation, play a central role in image understanding. Recent approaches have attempted to harness the capabilities of deep learning techniques for image recognition to tackle pixel-level labelling tasks. One central issue in this methodology is the limited capacity of deep learning techniques to delineate visual objects. To solve this problem, we introduce a new form of convolutional neural network that combines the strengths of Convolutional Neural Networks (CNNs) and Conditional Random Fields (CRFs)-based probabilistic graphical modelling. To this end, we formulate Conditional Random Fields with Gaussian pairwise potentials and mean-field approximate inference as Recurrent Neural Networks. This network, called CRF-RNN, is then plugged in as a part of a CNN to obtain a deep network that has desirable properties of both CNNs and CRFs. Importantly, our system fully integrates CRF modelling with CNNs, making it possible to train the whole deep network end-to-end with the usual back-propagation algorithm, avoiding offline post-processing methods for object delineation. We apply the proposed method to the problem of semantic image segmentation, obtaining top results on the challenging Pascal VOC 2012 segmentation benchmark.
PAF inhibitory activity of diketopiperazines: Structure‐activity relationships (1991)

FR900452, a natural product isolated from the culture broth of Streptomyces phaeofaciens No. 7739, was found to inhibit PAF-induced rabbit platelet aggregation with an IC50 of 3.7 x 10(-7)M. FR900452, 1-methyl-3-[1-[5- methylthiomethyl-6-oxo-3-(2-oxo-3-cyclopenten-1-yli- dene)-2-piperazinyl]ethyl]-2-indoline, has an oxocylopentylidene group incorporated as a vinylogous amide in a diketopiperazine skeleton. This unique structure led us to synthesize diketopiperazine derivatives, 3-arylalkyl- 6-substituted-piperazine-2,5-diones. Their observed PAF inhibitory activity suggest that the D-D configuration of diketopiperazine is an important factor for anti-PAF activity and that the hydrophobic aromatic portion may play a specific role in the binding of the diketopiperazine to the PAF receptor.
Neurons Overexpressing Heme Oxygenase‐1 Resist Oxidative Stress‐Mediated Cell Death (2000)

This is the first report on the protective effect of heme oxygenase-1 (HO-1) overexpression against oxidative stress-mediated neuronal cell death and demonstration of a decreased production of oxygen free radicals when HO-1 levels are increased. HO-1 is the heat shock/stress cognate of the heat shock protein 32 family of proteins. A known function of these proteins is alpha-meso bridge-specific cleavage of the heme molecule. For the present study, we used cerebellar granular neurons (CGNs) isolated from homozygous transgenic (Tg) mice that overexpress HO-1 under neuron-specific enolase control and nontransgenic (Ntg) littermates. The Tg mouse CGNs were characterized by increased levels of HO-1 mRNA and protein, a lower resting intracellular calcium concentration, and a reduced HO-1 transcriptional response to glutamate-mediated oxidative stress. Compared with the Ntg neurons, when exposed to glutamate (30 microM or 3 mM), the magnitude of cell viability was increased and the number of cells exhibiting membrane permeability and chromatin condensation were significantly decreased in the Tg CGN cultures. The population of neurons surviving glutamate toxicity decreased when HO-1 activity was inhibited by a peptide inhibitor. The neuroprotective effect by HO-1 was extended to H(2)O(2)-induced cell death. The mechanism of protection may involve in part a reduced production of reactive oxygen species upon exposure to glutamate. We suggest that induction of HO-1 by pharmacological means may be a novel approach to amelioration of oxidative insults to neurons.
Phosphoglucomutase Mutants of Escherichia coli K-12 (1971)

Bacteria with strongly depressed phosphoglucomutase (EC 2.7.5.1) activity are found among the mutants of Escherichia coli which, when grown on maltose, accumulate sufficient amylose to be detectable by iodine staining. These pgm mutants grow poorly on galactose but also accumulate amylose on this carbon source. Growth on lactose does not produce high amylose but, instead, results in the induction of the enzymes of maltose metabolism, presumably by accumulation of maltose. These facts suggest that the catabolism of glucose-1-phosphate is strongly depressed in pgm mutants, although not completely abolished. Anabolism of glucose-1-phosphate is also strongly depressed, since amino acid- or glucose-grown pgm mutants are sensitive to phage C21, indicating a deficiency in the biosynthesis of uridine diphosphoglucose or uridine diphosphogalactose, or both. All pgm mutations isolated map at about 16 min on the genetic map, between purE and the gal operon.