gebhart/patrepeval huggingface dataset:
A MODEL FOR DISEASE HETEROGENEITY IN SYSTEMIC LUPUS ERYTHEMATOSUS: Relationships Between Histocompatibility Antigens, Autoantibodies, and Lymphopenia or Renal Disease (1989)

We composed a model from autoimmune serologic findings, HLA antigens, and clinical findings that explains, at least partially, the clinical heterogeneity of 40 patients with systemic lupus erythematosus (SLE). In these patients, anti-RO (SS-A) was related to the HLA-DQ1/DQ2 heterozygotes, anti-La (SS-B) was related to HLA-B8 and HLA-DR3, and anti-nuclear RNP (Sm) was related to HLA-DR4. Lymphopenia was associated with anti-Ro (SS-A) and, secondarily, with anti-single-stranded DNA. Renal disease in these SLE patients was inversely associated with anti-La (SS-B) and was positively associated with anti-double-stranded DNA. There were no associations between the HLA antigens and these clinical manifestations. The results support a model of disease expression in which individuals are nonspecifically potentiated for SLE. Their HLA antigen composition influences the production of particular autoantibodies that are related in complex ways to the different particular clinical findings of SLE manifested in individual patients.
Far-red fluorescent tag for protein labelling (2002)

Practical applications of green fluorescent protein ('GFP')-like fluorescent proteins (FPs) from species of the class Anthozoa (sea anemones, corals and sea pens) are strongly restricted owing to their oligomeric nature. Here we suggest a strategy to overcome this problem by the use of two covalently linked identical red FPs as non-oligomerizing fusion tags. We have applied this approach to the dimeric far-red fluorescent protein HcRed1 and have demonstrated superiority of the tandem tag in the in vivo labelling of fine cytoskeletal structures and tiny nucleoli. In addition, a possibility of effective fluorescence resonance energy transfer ('FRET') between enhanced yellow FP mutant ('EYFP') and tandem HcRed1 was demonstrated in a protease assay.
Production of macrophage-derived cytotoxic factor by N-[3-[(carbamoylmethyl)thio]propionylated] neoglycoproteins (1991)

6-Phosphomannosylated bovine serum albumin (Man6P-BSA), a neoglycoprotein endocytosed by macrophages, bearing either 3-(2-pyridyldithio)propionyl or 3-[(carbamoylmethyl)thio]propionyl residues coming from alkylation of thiol residues by iodoacetamide were prepared and tested for their immunomodulator properties. The supernatants of mouse peritoneal macrophages incubated with Man6P-BSA bearing 3-[(carbamoylmethyl)thio]propionyl groups, and by a lesser extent 3-(2-pyridyldithio)propionyl groups, were cytotoxic to L929 cells, suggesting the presence of a tumor necrosis factor like compound. This macrophage-activation process is linked to the capacity of Man6P-BSA to be endocytosed via membrane lectins of macrophages, because the supernatants of macrophages incubated with unglycosylated conjugates were not cytotoxic. The cytotoxic activity induced by 3-[(carbamoylmethyl)thio]propionyl groups bound onto Man6P-BSA was similar to that induced by Man6P-BSA bearing muramyl dipeptide, indicating that endocytosed neoglycoproteins bearing 3-[(carbamoylmethyl)thio]propionyl residues are potent macrophage activators.
Raman on a disc: high-quality Raman spectroscopy in an open channel on a centrifugal microfluidic disc (2017)

The implausible combination of centrifugal disc microfluidics and un-covered channels provides a simple way in which Raman spectroscopy can be implemented in industrially-relevant lab-on-a disc technology. Here we demonstrate these advantages by detecting very low concentrations of melamine in liquid milk, without pre-processing, without surface enhancement of the Raman signal and with no evidence of spectral contamination from the polymeric chip itself. A limit of detection (LOD) of 203 ppm for melamine in milk was achieved from Raman spectra of milk after drying. The centrifugal disc rotation and microchannel geometry results in rapid and reliable filling of the channels and in meniscus shape control, enabling reproducible Raman detection with quantitative precision.
Recombinant transforming growth factor type beta 3: biological activities and receptor-binding properties in isolated bone cells. (1990)

We have recently cloned the cDNA for transforming growth factor type beta 3 (TGF-beta 3), a new member of the TGF-beta gene family. We examined the biological effects of recombinant TGF-beta 3 protein in osteoblast-enriched bone cell cultures. In this report we demonstrate that TGF-beta 3 is a potent regulator of functions associated with bone formation, i.e., mitogenesis, collagen synthesis, and alkaline phosphatase activity. In a direct comparison between TGF-beta 3 and TGF-beta 1, TGF-beta 3 appeared to be three- to fivefold more potent than TGF-beta 1. Our cross-linking experiments with iodinated TGF-beta showed that in osteoblast-enriched bone cell cultures, both TGF-beta 3 and TGF-beta 1 associated with the same three cell surface binding sites. Scatchard analysis of receptor competition studies indicated the presence of high-affinity binding sites for TGF-beta 3 in the picomolar range. TGF-beta 3 showed an approximately fourfold-higher apparent affinity than TGF-beta 1 in overall binding.
Selective Role of G Protein γ Subunits in Receptor Interaction (2000)

Receptor stimulation of nucleotide exchange in a heterotrimeric G protein (alphabetagamma) is the primary event-modulating signaling by G proteins. The molecular mechanisms at the basis of this event and the role of the G protein subunits, especially the betagamma complex, in receptor activation are unclear. In a reconstituted system, a purified muscarinic receptor, M2, activates G protein heterotrimers alphai2beta1gamma5 and alphai2beta1gamma7 with equal efficacy. However, when the alpha subunit type is substituted with alphao, alphaobeta1gamma7 shows a 100% increase in M2-stimulated GTP hydrolysis compared with alphaobeta1gamma5. Using a sensitive assay based on betagamma complex stimulation of phospholipase C activity, we show that both beta1gamma5 and beta1gamma7 form heterotrimers equally well with alphao and alphai. These results indicate that the gamma subunit interaction with a receptor is critical for modulating nucleotide exchange and is influenced by the subunit-type composition of the heterotrimer.
Myotilin is mutated in limb girdle muscular dystrophy 1A (2000)

We have identified a mutation in the myotilin gene in a large North American family of German descent expressing an autosomal dominant form of limb girdle muscular dystrophy (LGMD1A). We have previously mapped this gene to 5q31. Symptoms of this adult onset disease are progressive weakness of the hip and shoulder girdles, as well as a distinctive dysarthric pattern of speech. Muscle of affected individuals shows degeneration of myofibers, variations in fiber size, fiber splitting, centrally located myonuclei and a large number of autophagic vesicles. Affected muscle also exhibits disorganization and streaming of the Z-line similar to that seen in nemaline myopathy. We have identified a C450T missense mutation in the myotilin gene that is predicted to result in the conversion of residue 57 from threonine to isoleucine. This mutation has not been found in 396 control chromosomes. The mutant allele is transcribed and normal levels of correctly localized myotilin protein are seen in LGMD1A muscle. Myotilin is a sarcomeric protein that binds to alpha-actinin and is localized in the Z-line. The observed missense mutation does not disrupt binding to alpha-actinin.
A comparative study of IL-12 (cytotoxic lymphocyte maturation factor)-, IL-2-, and IL-7-induced effects on immunomagnetically purified CD56+ NK cells (1992)

IL-12, or cytotoxic lymphocyte maturation factor, is a recently cloned cytokine shown to influence lymphokine-activated killer cells activity in heterogeneous lymphocyte populations, proliferative activity as a costimulus in PBMC/PBL populations and IFN-gamma production in PBL. We have investigated the effects of IL-12 on immunomagnetically highly purified CD56+ lymphocytes, and compared the effects with those of IL-7 and IL-2. Our results show that IL-12 directly generated high lymphokine-activated killer cell activity in CD56+ NK cells, without the need for accessory cells. The IL-12-induced lymphokine-activated killer cell activity reached 50% of what was obtained with IL-2. In contrast, only low proliferative activity was induced by IL-12, as 10% of the IL-2-induced- and approximately 50% of the IL-7-induced proliferative activity was detected with IL-12. The CD56+ cells expressed high levels of IL-2R alpha and 75-kDa TNFR in response to IL-12, comparable to what was registered with IL-2 and IL-7. Furthermore, an extensive up-regulation of the CD56 Ag, to the level obtained with IL-2, was detected in the CD56+ NK cells in the presence of IL-12. Stimulation with IL-7 resulted in a more limited CD56 up-regulation in the CD56+ NK cells. Low concentrations of TNF-alpha were produced in response to both IL-12 and IL-7, with little or no TNF-beta production. Time course of the IL-2-induced TNF production revealed an initial TNF-alpha production, whereas significant levels of TNF-beta were detected after 72 h. The effects of both IL-12 and IL-7 on the CD56+ NK cells were inhibited by an anti-TNF-alpha mAb. Thus, IL-12 can directly influence NK cell activities in purified CD56+ cells, and endogenously produced TNF-alpha is involved in mediating the effects of both IL-12 and IL-7.
Induction of Humoral and Cellular Immune Responses to the Human Immunodeficiency Type 1 Virus in Nonhuman Primates by in Vivo DNA Inoculation (1995)

DNA inoculation has the potential to produce antigens in a native as well as a host-"customized" form for presentation to the immune system. As such this technology may have relevance for vaccine/immune therapeutic strategies for a variety of infectious pathogens. In rodents in vivo inoculation of plasmid expression vectors encoding HIV-1 gene products leads to production of HIV-1 antigens in vivo, resulting in the production of both cellular and humoral immune responses. In primates only preliminary studies of serology have been reported. Here we report further evaluation of this new technology as a method to induce humoral and particularly cellular immune responses against a human pathogen, the HIV-1 virus, in nonhuman primates. Following inoculation and boosting of animals with an HIV gp160 plasmid expression vector we observed the induction of neutralizing responses against two diverse HIV-1 isolates in 2 of 3 vaccinated animals. T cell proliferative responses to HIV antigens were also observed in all plasmid-inoculated animals and specific cross-reactive cytotoxic T lymphocyte responses were developed in vaccinated animals. This report establishes the ability of DNA inoculation to induce cellular immune responses in nonhuman primates and suggests that further investigation of this technology with regard to human vaccine or immune therapeutic development is therefore warranted.
A novel strategy for production of a highly expressed recombinant protein in an active form (1991)

Under standard growth conditions, E. coli transformed with the high-level expression vector pMON5525 produces recombinant DMAPP/AMP transferase in inactive, insoluble complexes. We have produced large amounts of active, soluble protein by growing and inducing the cells under osmotic stress in the presence of sorbitol and glycyl betaine. This caused an increase of up to 427-fold in the active yield, and the disappearance of the protein from the pelletable fraction of cell extracts. This treatment may have wide applicability.
Tissue engineering strategies for in vivo neovascularisation (2002)

Neovascularisation is a promising alternative therapeutic approach to re-establish blood flow in ischaemic tissues of patients suffering from coronary artery or peripheral artery disease. Often, these patients are not suitable candidates for current revascularisation procedures such as coronary angioplasty or bypass surgery. Several strategies are presently under investigation to induce vascularisation by stimulating the body's natural processes of vasculogenesis, angiogenesis and arteriogenesis. These strategies involve transplantation of various cell types into the ischaemic site and the delivery of recombinant angiogenic agents through direct protein administration or gene transfer. We will examine the basic approaches for these neovacularisation strategies and their therapeutic potential as demonstrated in animal models and human trials to date.
Endocrine ,neuroendocrine and behavioral effects of oral dehydroepiandrosterone sulfate supplementation in postmenopausal women (1999)

Aging in women and men is characterized by a progressive decline of circulating dehydroepiandrosterone (DHEA) levels and its sulfate ester (DHEAS). The improvement of wellbeing described in postmenopausal women treated with DHEA suggests that this steroid may exert specific actions on the central nervous system (CNS). The postmenopausal period is associated with several neuroendocrine modifications. The decrease of circulating levels of beta-endorphin is considered a hormonal marker of those changes. The aim of the present study was to investigate neuroendocrine and behavioral effects of three months of DHEAS supplementation in postmenopausal women. Postmenopausal women (n = 22) were divided in three groups: the first group was treated with oral DHEAS (n = 8) (50 mg/day), the second treated with the same dose of oral DHEAS + transdermal estradiol (n = 8) (DHEAS) 50 mg/day, estradiol 50 micrograms/patch) and the third with transdermal estradiol alone (n = 6) (50 micrograms/day). Before and after 1, 2 and 3 months of therapy, the following circulating steroid and protein hormone levels were evaluated: DHEA, DHEAS, androstenedione, testosterone, estrone, estradiol, 17-hydroxyprogesterone, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), beta-endorphin, growth hormone (GH) and cortisol, and a Kupperman score was performed. Before and after treatments, plasma beta-endorphin levels were evaluated in response to three neuroendocrine tests: (a) clonidine, an alpha 2-presynaptic adrenergic agonist (1.25 mg i.v.) (b) naloxone, an opioid receptor antagonist (4 mg i.v.) and (c) fluoxetine, a serotonin selective reuptake inhibitor (30 mg p.o.). In both groups of women treated with DHEAS, mean basal serum DHEA, DHEAS, androstenedione, and testosterone levels significantly increased after treatment, while no changes were shown in the group receiving estradiol alone. Serum estradiol, estrone, GH and plasma beta-endorphin levels significantly increased progressively for the three months of treatment, with higher levels for estrone and estradiol in subjects receiving estradiol alone or plus DHEAS. Serum SHBG, cortisol, and 17-hydroxyprogesterone did not show significant variations under any treatment. Serum LH and FSH levels showed a significant decrease in groups treated with estradiol alone or plus DHEAS at the second and third months. The Kupperman score showed that all treatments were associated with similar and progressive improvement. Before therapy clonidine, naloxone and fluoxetine stimuli failed to modify circulating beta-endorphin levels. After each of the treatments, the beta-endorphin response was completely restored and was similar, independent of the kind of therapy. Restoration of the beta-endorphin response to specific stimuli suggests that DHEAS and/or its active metabolites modulates the neuroendocrine control of pituitary beta-endorphin secretion, which may support the therapeutic efficacy of the DHEAS on behavioral symptoms.
Fungal Peritonitis Complicating Peritoneal Dialysis during an 11‐Year Period: Report of 46 Cases (2003)

The incidence of fungal peritonitis (FP) and the fungi that caused FP were evaluated in 422 patients treated with peritoneal dialysis. During an 11-year period, 804 episodes of peritonitis occurred, 46 (5.7%) of which were caused by fungi. Treatment was successful for 39 patients. Early diagnosis of FP and prompt therapy decreases morbidity and mortality.
Leptin Induces Endothelial Cell Migration Through Akt, Which Is Inhibited by PPARγ-Ligands (2002)

Migration of endothelial cells (EC) is a key event in angiogenesis that contributes to neovascularization in diabetic vasculopathy. Leptin induces angiogenesis and is elevated in obesity and hyperinsulinemia. The antidiabetic thiazolidinediones (TZD) inhibit leptin gene expression and vascular smooth muscle cell migration through activation of the peroxisome proliferator-activated receptor-gamma (PPARgamma). This study investigates the role of leptin in EC migration, the chemotactic signaling pathways involved, and the effects of the TZD-PPARgamma ligands troglitazone (TRO) and ciglitazone (CIG) on EC migration. We demonstrate that leptin induces EC migration. Because activation of two signaling pathways, the phosphatidylinositol-3 kinase (PI3K)-->Akt-->eNOS and the ERK1/2 MAPK pathway, is known to be involved in cell migration, we used the pharmacological inhibitors wortmannin and PD98059 to determine if chemotactic signaling by leptin involves Akt or ERK1/2, respectively. Both wortmannin and PD98059 significantly inhibited leptin-induced migration. Treatment with the TZD-PPARgamma-ligands TRO and CIG significantly inhibited the chemotactic response toward leptin. Both PPARgamma-ligands inhibited leptin-stimulated Akt and eNOS phosphorylation, but neither attenuated ERK 1/2 activation in response to leptin. The inhibition of Akt-phosphorylation was accompanied by a PPARgamma-ligand-mediated upregulation of PTEN, a phosphatase that functions as a negative regulator of PI3K-->Akt signaling. These experiments provide the first evidence that activation of Akt and ERK 1/2 are crucial events in leptin-mediated signal transduction leading to EC migration. Moreover, inhibition of leptin-directed migration by the PPARgamma-ligands TRO and CIG through inhibition of Akt underscores their potential in the prevention of diabetes-associated complications.
Grape-II: a system-level prototyping environment for DSP applications (1995)

We propose a rapid-prototyping setup to minimize development cost and a structured-prototyping methodology to reduce programming effort. The general-purpose hardware consists of commercial DSP processors, bond-out versions of core processors, and field-programmable gate arrays (FPGAs) linked to form a powerful, heterogeneous multiprocessor, such as the Paradigm RP developed within the Retides (Real-Time DSP Emulation System) Esprit project. Our Graphical Rapid Prototyping Environment (Grape-II) automates the prototyping methodology for these hardware systems by offering tools for resource estimation, partitioning, assignment, routing, scheduling, code generation, and parameter modification. Grape-II has been used successfully in three real-world DSP applications.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The N-terminal cysteine of human asparagine synthetase is essential for glutamine-dependent activity (1989)

Site-specific mutagenesis was used to replace the N-terminal cysteine in human asparagine synthetase by an alanine. The mutant enzyme was expressed in the yeast Saccharomyces cerevisiae, and the asparagine synthetase activity was analyzed in vitro. The mutation resulted in the loss of the glutamine-dependent asparagine synthetase activity, while the ammonia-dependent activity remained unaffected. These results confirm the existence of a glutamine amidotransfer domain with an N-terminal cysteine essential for the glutamine-dependent asparagine synthetase activity.
Morris Water Maze Test for Learning and Memory Deficits in Alzheimer's Disease Model Mice (2011)

The Morris Water Maze (MWM) was first established by neuroscientist Richard G. Morris in 1981 in order to test hippocampal-dependent learning, including acquisition of spatial memory and long-term spatial memory. The MWM is a relatively simple procedure typically consisting of six day trials, the main advantage being the differentiation between the spatial (hidden-platform) and non-spatial (visible platform) conditions. In addition, the MWM testing environment reduces odor trail interference. This has led the task to be used extensively in the study of the neurobiology and neuropharmacology of spatial learning and memory. The MWM plays an important role in the validation of rodent models for neurocognitive disorders such as Alzheimer's Disease. In this protocol we discussed the typical procedure of MWM for testing learning and memory and data analysis commonly used in Alzheimer's disease transgenic model mice.
Pathogenesis of Ovarian Cancer (2008)

The accepted view of ovarian carcinogenesis is that carcinoma begins in the ovary, undergoes progressive "dedifferentiation" from a well to a poorly differentiated tumor, and then spreads to the pelvic and abdominal cavities before metastasizing to distant sites. It has therefore been reasoned that survival for this highly lethal disease could be improved by developing screening methods that detect disease when it is confined to the ovary. To date, however, no prospective randomized trial of any ovarian cancer screening test(s) has demonstrated a decrease in mortality. We believe that one of the main reasons for this is that the dogma underlying ovarian carcinogenesis is flawed. Based on studies performed in our laboratory during the last decade, we have proposed a model of ovarian carcinogenesis that takes into account the diverse nature of ovarian cancer and correlates the clinical, pathological, and molecular features of the disease. In this model, ovarian tumors are divided into 2 groups designated type I and type II. Type I tumors are slow growing, generally confined to the ovary at diagnosis, and develop from well-established precursor lesions that are termed "borderline" tumors. Type I tumors include low-grade micropapillary serous carcinoma, mucinous, endometrioid, and clear cell carcinomas. They are genetically stable and are characterized by mutations in a number of different genes including KRAS, BRAF, PTEN, and beta-catenin. Type II tumors are rapidly growing highly aggressive neoplasms for which well-defined precursor lesions have not been described. Type II tumors include high-grade serous carcinoma, malignant mixed mesodermal tumors (carcinosarcomas), and undifferentiated carcinomas. This group of tumors has a high level of genetic instability and is characterized by mutation of TP53. The model helps to explain why current screening techniques, aimed at detecting stage I disease, have not been effective. Tumors that remain confined to the ovary for a long period belong to the type I group, but they account for only 25% of the malignant tumors. Most of what is considered ovarian cancer belongs to the type II category, and these are only rarely confined to the ovary. Although the reasons for this are not entirely clear, possible explanations include rapid spread from the ovary early in carcinogenesis and development of carcinoma in extra ovarian sites, notably, the peritoneum and fallopian tube, with secondary involvement of the ovary. The latter tumors are advanced stage at their inception. Therefore, a more realistic end point for the early detection of ovarian cancer is volume and not stage of disease. The model does not replace the histopathologic classification but, by drawing attention to the molecular genetic events that play a role in tumor progression, sheds light on new approaches to early detection and treatment.